6-148486077-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.628-1537T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,176 control chromosomes in the GnomAD database, including 2,497 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 0.17 (2497 hom., cov: 33)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SASH1	NM_015278.5	c.628-1537T>C		intron_variant		ENST00000367467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SASH1	ENST00000367467.8	c.628-1537T>C		intron_variant		1	NM_015278.5	P1
SASH1	ENST00000637469.1	c.73-1537T>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25436 AN: 152058 Hom.: 2490 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.167 AC: 25451 AN: 152176 Hom.: 2497 Cov.: 33 AF XY: 0.167 AC XY: 12398 AN XY: 74400

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.161

Alfa AF: 0.117 Hom.: 1206

Bravo AF: 0.168

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.4
Dann	Benign	0.46

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: rs11961740; hg19: chr6-148807213; COSMIC: COSV66565241;