Variant 6-148343268-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.156+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,530,962 control chromosomes in the GnomAD database, including 10,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.085 ( 745 hom., cov: 32)

Exomes 𝑓: 0.12 ( 9866 hom. )

Consequence

SASH1
NM_015278.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.419

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=-0.8).

BP6

Variant 6-148343268-G-A is Benign according to our data. Variant chr6-148343268-G-A is described in ClinVar as [Benign]. Clinvar id is 1251256.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 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.156+45G>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.156+45G>A		intron_variant		1	NM_015278.5	P1
SASH1	ENST00000367469.5 linkuse as main transcript	n.75-46866G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0847

AC:

12886

AN:

152118

Hom.:

745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0562

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0892

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.0865

GnomAD3 exomes

AF:

0.0932

AC:

19023

AN:

204200

Hom.:

1124

AF XY:

0.0984

AC XY:

11145

AN XY:

113258

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.0388

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.000289

Gnomad SAS exome

AF:

0.0917

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.0977

GnomAD4 exome

AF:

0.115

AC:

158847

AN:

1378726

Hom.:

9866

Cov.:

AF XY:

0.115

AC XY:

78700

AN XY:

681938

show subpopulations

Gnomad4 AFR exome

AF:

0.0193

Gnomad4 AMR exome

AF:

0.0435

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.000256

Gnomad4 SAS exome

AF:

0.0921

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.0981

GnomAD4 genome

AF:

0.0846

AC:

12886

AN:

152236

Hom.:

745

Cov.:

AF XY:

0.0830

AC XY:

6175

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0232

Gnomad4 AMR

AF:

0.0562

Gnomad4 ASJ

AF:

0.0988

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0895

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.0851

Alfa

AF:

0.104

Hom.:

274

Bravo

AF:

0.0764

Asia WGS

AF:

0.0530

AC:

183

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

-0.80

CADD

Benign

6.8

DANN

Benign

0.78

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