Variant rs4963 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001354761.2(ADD1):c.1943C>G(p.Ser648Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,610,858 control chromosomes in the GnomAD database, including 32,157 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 2889 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29268 hom. )

Consequence

ADD1
NM_001354761.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.816255E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADD1	NM_001354761.2 linkuse as main transcript	c.1943C>G	p.Ser648Cys	missense_variant	14/16	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.1943C>G	p.Ser648Cys	missense_variant	14/16		NM_001354761.2	ENSP00000508142.1		A0A804HL01

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28344

AN:

152060

Hom.:

2884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.161

GnomAD3 exomes

AF:

0.204

AC:

49926

AN:

245190

Hom.:

5862

AF XY:

0.199

AC XY:

26366

AN XY:

132584

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.468

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.191

AC:

279106

AN:

1458680

Hom.:

29268

Cov.:

AF XY:

0.189

AC XY:

137409

AN XY:

725510

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.173

Gnomad4 FIN exome

AF:

0.183

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.186

AC:

28379

AN:

152178

Hom.:

2889

Cov.:

AF XY:

0.187

AC XY:

13899

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.167

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.478

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.176

Hom.:

755

Bravo

AF:

0.190

TwinsUK

AF:

0.191

AC:

707

ALSPAC

AF:

0.186

AC:

716

ESP6500AA

AF:

0.176

AC:

777

ESP6500EA

AF:

0.184

AC:

1582

ExAC

AF:

0.202

AC:

24543

Asia WGS

AF:

0.332

AC:

1155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.019

.;.;T;T;.;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.37

T;T;T;T;T;.;T

MetaRNN

Benign

0.00078

T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.90

.;.;.;.;.;.;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.94

N;N;N;N;N;N;N

REVEL

Benign

0.089

Sift

Benign

0.054

T;T;T;T;T;T;T

Sift4G

Uncertain

0.053

T;T;T;T;T;T;T

Polyphen

0.94

P;.;.;.;.;.;B

Vest4

0.096

MPC

0.66

ClinPred

0.026

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.074

gMVP

0.092

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over