Variant 6-148540580-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015278.5(SASH1):c.2209+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,561,418 control chromosomes in the GnomAD database, including 15,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1584 hom., cov: 31)

Exomes 𝑓: 0.14 ( 13629 hom. )

Consequence

SASH1
NM_015278.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.678

Variant links:

Genes affected

SASH1 (HGNC:19182): (SAM and SH3 domain containing 1) This gene encodes a scaffold protein involved in the TLR4 signaling pathway that may stimulate cytokine production and endothelial cell migration in response to invading pathogens. The encoded protein has also been described as a potential tumor suppressor that may negatively regulate proliferation, apoptosis, and invasion of cancer cells, and reduced expression of this gene has been observed in multiple human cancers. Mutations in this gene may be associated with abnormal skin pigmentation in human patients. [provided by RefSeq, Oct 2016]

SASH1 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 (BayesDel_noAF=-0.81).

BP6

Variant 6-148540580-G-A is Benign according to our data. Variant chr6-148540580-G-A is described in ClinVar as [Benign]. Clinvar id is 1285745.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SASH1	NM_015278.5 linkuse as main transcript	c.2209+24G>A		intron_variant		ENST00000367467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SASH1	ENST00000367467.8 linkuse as main transcript	c.2209+24G>A		intron_variant		1	NM_015278.5	P1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21458

AN:

151970

Hom.:

1584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.126

GnomAD3 exomes

AF:

0.139

AC:

33151

AN:

238624

Hom.:

2370

AF XY:

0.140

AC XY:

18011

AN XY:

128928

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.115

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.137

AC:

192561

AN:

1409330

Hom.:

13629

Cov.:

AF XY:

0.137

AC XY:

96134

AN XY:

703658

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.0813

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.141

AC:

21459

AN:

152088

Hom.:

1584

Cov.:

AF XY:

0.144

AC XY:

10667

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.143

Hom.:

2474

Bravo

AF:

0.132

Asia WGS

AF:

0.111

AC:

385

AN:

3478

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

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

DANN

Benign

0.83

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