rs1147857

Positions:

• chr6-148520616-T-C

Variant summary

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

The NM_015278.5(SASH1):​c.1209+723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,882 control chromosomes in the GnomAD database, including 16,680 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 0.45 (16680 hom., cov: 31)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SASH1	NM_015278.5	c.1209+723T>C		intron_variant		ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SASH1	ENST00000367467.8	c.1209+723T>C		intron_variant		1	NM_015278.5	ENSP00000356437	P1
SASH1	ENST00000636279.1	c.969+234T>C		intron_variant		5		ENSP00000490865

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69042 AN: 151762 Hom.: 16683 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.455 AC: 69055 AN: 151882 Hom.: 16680 Cov.: 31 AF XY: 0.458 AC XY: 33956 AN XY: 74218

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.478

Alfa AF: 0.507 Hom.: 39268

Bravo AF: 0.440

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.75

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: rs1147857; hg19: chr6-148841752;