chr20-44632053-C-T

Variant names:

• chr20-44632053-C-T
• rs379863
• NM_000022.4:c.96-2884G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000022.4(ADA):​c.96-2884G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,138 control chromosomes in the GnomAD database, including 41,730 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (41730 hom., cov: 32)
• Consequence: ADA NM_000022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

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

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA	NM_000022.4	c.96-2884G>A		intron_variant	Intron 2 of 11	ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2	c.96-2884G>A		intron_variant	Intron 2 of 10		NP_001308980.1
ADA	NM_001322050.2	c.-194-2884G>A		intron_variant	Intron 2 of 10		NP_001308979.1
ADA	NR_136160.2	n.188-2884G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADA	ENST00000372874.9	c.96-2884G>A		intron_variant	Intron 2 of 11	1	NM_000022.4	ENSP00000361965.4
ADA	ENST00000695995.1	c.96-2884G>A		intron_variant	Intron 2 of 8			ENSP00000512318.1
ADA	ENST00000695991.1	c.96-2884G>A		intron_variant	Intron 2 of 7			ENSP00000512314.1
ADA	ENST00000696038.1	n.96-2884G>A		intron_variant	Intron 2 of 8			ENSP00000512344.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111478 AN: 152020 Hom.: 41726 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.733 AC: 111512 AN: 152138 Hom.: 41730 Cov.: 32 AF XY: 0.732 AC XY: 54413 AN XY: 74354

African (AFR) AF: 0.582 AC: 24125 AN: 41478

American (AMR) AF: 0.647 AC: 9904 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2764 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4283 AN: 5146

South Asian (SAS) AF: 0.738 AC: 3562 AN: 4826

European-Finnish (FIN) AF: 0.802 AC: 8498 AN: 10596

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55833 AN: 67996

Other (OTH) AF: 0.731 AC: 1545 AN: 2114

Alfa AF: 0.786 Hom.: 85760

Bravo AF: 0.715

Asia WGS AF: 0.742 AC: 2581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.060
DANN	Benign	0.71
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs379863; hg19: chr20-43260694;