rs6909677

chr6-148540580-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.678

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]

ACMG classification

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	c.2209+24G>A		intron_variant		ENST00000367467.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21458 AN: 151970 Hom.: 1584 Cov.: 31

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

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.: 22 AF XY: 0.137 AC XY: 96134 AN XY: 703658

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.: 31 AF XY: 0.144 AC XY: 10667 AN XY: 74314

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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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

Other links and lift over

dbSNP: rs6909677; hg19: chr6-148861716; COSMIC: COSV66561792;