Variant 7-38394163-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001635.4(AMPH):c.1450G>T(p.Ala484Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,614,242 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 9 hom. )

Consequence

AMPH
NM_001635.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.186

Variant links:

Genes affected

AMPH (HGNC:471): (amphiphysin) This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff-man syndrome who were also affected by breast cancer are positive for autoantibodies against this protein. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences have not been determined. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Nov 2010]

AMPH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003232807).

BP6

Variant 7-38394163-C-A is Benign according to our data. Variant chr7-38394163-C-A is described in ClinVar as [Benign]. Clinvar id is 731328.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00611 (931/152358) while in subpopulation AFR AF= 0.0212 (881/41578). AF 95% confidence interval is 0.02. There are 12 homozygotes in gnomad4. There are 457 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPH	NM_001635.4 linkuse as main transcript	c.1450G>T	p.Ala484Ser	missense_variant	18/21	ENST00000356264.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPH	ENST00000356264.7 linkuse as main transcript	c.1450G>T	p.Ala484Ser	missense_variant	18/21	1	NM_001635.4	P3	P49418-1

Frequencies

GnomAD3 genomes

AF:

0.00612

AC:

931

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00155

AC:

390

AN:

251418

Hom.:

AF XY:

0.00118

AC XY:

160

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000590

AC:

862

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

369

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0213

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00611

AC:

931

AN:

152358

Hom.:

Cov.:

AF XY:

0.00613

AC XY:

457

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0212

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00681

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0184

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00203

AC:

246

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

Cadd

Benign

7.0

Dann

Benign

0.88

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.059

Sift

Benign

0.27

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.015

B;B

Vest4

0.10

MVP

0.66

MPC

0.21

ClinPred

0.0034

GERP RS

2.5

Varity_R

0.046

gMVP

0.098

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