Variant 6-148440320-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015278.5(SASH1):c.337-38G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,611,128 control chromosomes in the GnomAD database, including 146,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13727 hom., cov: 30)

Exomes 𝑓: 0.42 ( 132404 hom. )

Consequence

SASH1
NM_015278.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.88

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-148440320-G-C is Benign according to our data. Variant chr6-148440320-G-C is described in ClinVar as [Benign]. Clinvar id is 1289486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SASH1	NM_015278.5 linkuse as main transcript	c.337-38G>C		intron_variant		ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
SASH1	ENST00000367467.8 linkuse as main transcript	c.337-38G>C	intron_variant	1	NM_015278.5	ENSP00000356437	P1
SASH1	ENST00000367469.5 linkuse as main transcript	n.255-38G>C	intron_variant, non_coding_transcript_variant	3
SASH1	ENST00000470750.1 linkuse as main transcript		upstream_gene_variant	3

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

63932

AN:

151476

Hom.:

13719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.391

GnomAD3 exomes

AF:

0.446

AC:

111954

AN:

251268

Hom.:

26059

AF XY:

0.456

AC XY:

61890

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.404

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.669

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.419

GnomAD4 exome

AF:

0.421

AC:

614296

AN:

1459534

Hom.:

132404

Cov.:

AF XY:

0.428

AC XY:

310633

AN XY:

726266

show subpopulations

Gnomad4 AFR exome

AF:

0.419

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.426

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.663

Gnomad4 FIN exome

AF:

0.460

Gnomad4 NFE exome

AF:

0.400

Gnomad4 OTH exome

AF:

0.423

GnomAD4 genome

AF:

0.422

AC:

63970

AN:

151594

Hom.:

13727

Cov.:

AF XY:

0.430

AC XY:

31832

AN XY:

74048

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.414

Gnomad4 SAS

AF:

0.682

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.406

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.421

Hom.:

2462

Bravo

AF:

0.410

Asia WGS

AF:

0.538

AC:

1870

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Dyschromatosis universalis hereditaria 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.59

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