Variant 4-2894692-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001354761.2(ADD1):c.702G>A(p.Val234Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,601,210 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 17 hom. )

Consequence

ADD1
NM_001354761.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.960

Variant links:

Genes affected

ADD1 (HGNC:243): (adducin 1) Adducins are a family of cytoskeletal proteins encoded by three genes (alpha, beta, and gamma). Adducin acts as a heterodimer of the related alpha, beta, or gamma subunits. The protein encoded by this gene represents the alpha subunit. Alpha- and beta-adducin include a protease-resistant N-terminal region and a protease-sensitive, hydrophilic C-terminal region. Adducin binds with high affinity to Ca(2+)/calmodulin and is a substrate for protein kinases A and C. [provided by RefSeq, Aug 2017]

ADD1 links:

ADD1 (HGNC:):

ADD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 4-2894692-G-A is Benign according to our data. Variant chr4-2894692-G-A is described in ClinVar as [Benign]. Clinvar id is 789993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.96 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00879 (1339/152268) while in subpopulation AFR AF= 0.0304 (1262/41550). AF 95% confidence interval is 0.029. There are 16 homozygotes in gnomad4. There are 594 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADD1	NM_001354761.2 linkuse as main transcript	c.702G>A	p.Val234Val	synonymous_variant	6/16	ENST00000683351.1	NP_001341690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADD1	ENST00000683351.1 linkuse as main transcript	c.702G>A	p.Val234Val	synonymous_variant	6/16		NM_001354761.2	ENSP00000508142.1		A0A804HL01

Frequencies

GnomAD3 genomes

AF:

0.00873

AC:

1329

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00229

AC:

541

AN:

236010

Hom.:

AF XY:

0.00172

AC XY:

220

AN XY:

127674

show subpopulations

Gnomad AFR exome

AF:

0.0296

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.000413

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000751

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.00172

GnomAD4 exome

AF:

0.000890

AC:

1289

AN:

1448942

Hom.:

Cov.:

AF XY:

0.000824

AC XY:

594

AN XY:

720562

show subpopulations

Gnomad4 AFR exome

AF:

0.0305

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000844

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000613

Gnomad4 OTH exome

AF:

0.00254

GnomAD4 genome

AF:

0.00879

AC:

1339

AN:

152268

Hom.:

Cov.:

AF XY:

0.00798

AC XY:

594

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0304

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00299

Hom.:

Bravo

AF:

0.00996

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.6

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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