rs9497965

Positions:

• chr6-148200156-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017010599.2(SASH1):​c.45+6531C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,078 control chromosomes in the GnomAD database, including 12,120 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12120 hom., cov: 33)
• Consequence: SASH1 XM_017010599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SASH1	XM_017010599.2	c.45+6531C>T		intron_variant			XP_016866088.1
SASH1	XM_024446384.2	c.45+6531C>T		intron_variant			XP_024302152.1
		n.148200156C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60377 AN: 151960 Hom.: 12113 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.422

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60420 AN: 152078 Hom.: 12120 Cov.: 33 AF XY: 0.394 AC XY: 29303 AN XY: 74336

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.418

Alfa AF: 0.389 Hom.: 1543

Bravo AF: 0.404

Asia WGS AF: 0.404 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9497965; hg19: chr6-148521292; COSMIC: COSV60291159;