rs61737144

Positions:

chr20-44625657-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000022.4(ADA):c.390G>A(p.Val130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,570,220 control chromosomes in the GnomAD database, including 1,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 141 hom., cov: 32)

Exomes 𝑓: 0.034 ( 871 hom. )

Consequence

ADA
NM_000022.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

ADA (HGNC:186): (adenosine deaminase) This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway. Various mutations have been described for this gene and have been linked to human diseases related to impaired immune function such as severe combined immunodeficiency disease (SCID) which is the result of a deficiency in the ADA enzyme. In ADA-deficient individuals there is a marked depletion of T, B, and NK lymphocytes, and consequently, a lack of both humoral and cellular immunity. Conversely, elevated levels of this enzyme are associated with congenital hemolytic anemia. [provided by RefSeq, Sep 2019]

ADA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 20-44625657-C-T is Benign according to our data. Variant chr20-44625657-C-T is described in ClinVar as [Benign]. Clinvar id is 35653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADA	NM_000022.4 linkuse as main transcript	c.390G>A	p.Val130=	synonymous_variant	5/12	ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2 linkuse as main transcript	c.390G>A	p.Val130=	synonymous_variant	5/11		NP_001308980.1
ADA	NM_001322050.2 linkuse as main transcript	c.73+799G>A		intron_variant			NP_001308979.1
ADA	NR_136160.2 linkuse as main transcript	n.482G>A		non_coding_transcript_exon_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADA	ENST00000372874.9 linkuse as main transcript	c.390G>A	p.Val130=	synonymous_variant	5/12	1	NM_000022.4	ENSP00000361965	P4

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6056

AN:

152178

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0581

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.0449

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0350

Gnomad OTH

AF:

0.0383

GnomAD3 exomes

AF:

0.0301

AC:

5382

AN:

179032

Hom.:

AF XY:

0.0296

AC XY:

2825

AN XY:

95396

show subpopulations

Gnomad AFR exome

AF:

0.0618

Gnomad AMR exome

AF:

0.0166

Gnomad ASJ exome

AF:

0.0452

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.0181

Gnomad FIN exome

AF:

0.0412

Gnomad NFE exome

AF:

0.0354

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0337

AC:

47801

AN:

1417924

Hom.:

871

Cov.:

AF XY:

0.0331

AC XY:

23236

AN XY:

701200

show subpopulations

Gnomad4 AFR exome

AF:

0.0593

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0415

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.0171

Gnomad4 FIN exome

AF:

0.0429

Gnomad4 NFE exome

AF:

0.0352

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0398

AC:

6063

AN:

152296

Hom.:

141

Cov.:

AF XY:

0.0390

AC XY:

2907

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0582

Gnomad4 AMR

AF:

0.0309

Gnomad4 ASJ

AF:

0.0432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.0449

Gnomad4 NFE

AF:

0.0350

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0374

Hom.:

Bravo

AF:

0.0394

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Benign:4

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, silent variant not near splice site, 2 labs submitted as benign to clinvar -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Severe combined immunodeficiency disease

Benign:1

Benign, criteria provided, single submitter

clinical testing;curation

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 18, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.8

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over