rs6930576

chr6-148383818-G-Achr6-148383818-G-T

Variant summary

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

The NM_015278.5(SASH1):c.157-6316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,980 control chromosomes in the GnomAD database, including 9,981 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 0.36 (9981 hom., cov: 32)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SASH1	NM_015278.5	c.157-6316G>A		intron_variant		ENST00000367467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SASH1	ENST00000367467.8	c.157-6316G>A		intron_variant		1	NM_015278.5	P1
SASH1	ENST00000367469.5	n.75-6316G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54248 AN: 151864 Hom.: 9959 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.357 AC: 54300 AN: 151980 Hom.: 9981 Cov.: 32 AF XY: 0.350 AC XY: 26007 AN XY: 74298

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.383

Alfa AF: 0.378 Hom.: 14485

Bravo AF: 0.365

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.52
Dann	Benign	0.80

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

Other links and lift over

dbSNP: rs6930576; hg19: chr6-148704954;