rs17712470

Positions:

• chr6-148371999-C-A
• chr6-148371999-C-T

Variant summary

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

The NM_015278.5(SASH1):​c.157-18135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,898 control chromosomes in the GnomAD database, including 5,386 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 0.26 (5386 hom., cov: 32)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SASH1	NM_015278.5	c.157-18135C>A		intron_variant		ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SASH1	ENST00000367467.8	c.157-18135C>A		intron_variant		1	NM_015278.5	ENSP00000356437	P1
SASH1	ENST00000367469.5	n.75-18135C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39549 AN: 151780 Hom.: 5389 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.260 AC: 39541 AN: 151898 Hom.: 5386 Cov.: 32 AF XY: 0.261 AC XY: 19380 AN XY: 74248

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.252

Alfa AF: 0.190 Hom.: 528

Bravo AF: 0.248

Asia WGS AF: 0.145 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.58

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: rs17712470; hg19: chr6-148693135;