Variant 4-2875960-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001354761.2(ADD1):c.45G>T(p.Pro15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000801 in 1,613,398 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 4 hom. )

Consequence

ADD1
NM_001354761.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.298

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 4-2875960-G-T is Benign according to our data. Variant chr4-2875960-G-T is described in ClinVar as [Benign]. Clinvar id is 790308.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.298 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADD1	NM_001354761.2 linkuse as main transcript	c.45G>T	p.Pro15=	synonymous_variant	2/16	ENST00000683351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADD1	ENST00000683351.1 linkuse as main transcript	c.45G>T	p.Pro15=	synonymous_variant	2/16		NM_001354761.2

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00104

AC:

260

AN:

250708

Hom.:

AF XY:

0.00101

AC XY:

137

AN XY:

135480

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00329

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000950

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000802

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.000765

AC:

1118

AN:

1461132

Hom.:

Cov.:

AF XY:

0.000798

AC XY:

580

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00332

Gnomad4 ASJ exome

AF:

0.000345

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000883

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000606

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00114

AC:

174

AN:

152266

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000772

Hom.:

Bravo

AF:

0.00136

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000765

EpiControl

AF:

0.000949

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.8

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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