Variant 4-2898279-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001354761.2(ADD1):c.837T>C(p.Asp279Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00074 in 1,614,172 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 4 hom. )

Consequence

ADD1
NM_001354761.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.502

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 4-2898279-T-C is Benign according to our data. Variant chr4-2898279-T-C is described in ClinVar as [Benign]. Clinvar id is 790309.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.502 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADD1	NM_001354761.2 linkuse as main transcript	c.837T>C	p.Asp279Asp	synonymous_variant	7/16	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.837T>C	p.Asp279Asp	synonymous_variant	7/16		NM_001354761.2	ENSP00000508142.1		A0A804HL01

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000966

AC:

243

AN:

251468

Hom.:

AF XY:

0.000905

AC XY:

123

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000703

AC:

1028

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000723

AC XY:

526

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000546

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152278

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000935

Hom.:

Bravo

AF:

0.00126

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.50

CADD

Benign

6.1

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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