6-148350012-A-C

Position:

• chr6-148350012-A-C

Variant summary

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

The NM_015278.5(SASH1):​c.156+6789A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,722 control chromosomes in the GnomAD database, including 3,906 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 0.21 (3906 hom., cov: 31)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99

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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SASH1	NM_015278.5	c.156+6789A>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.156+6789A>C		intron_variant		1	NM_015278.5	ENSP00000356437	P1
SASH1	ENST00000367469.5	n.75-40122A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32441 AN: 151604 Hom.: 3910 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.214 AC: 32445 AN: 151722 Hom.: 3906 Cov.: 31 AF XY: 0.209 AC XY: 15520 AN XY: 74114

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.224

Alfa AF: 0.236 Hom.: 556

Bravo AF: 0.207

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.11

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: rs11155563; hg19: chr6-148671148; COSMIC: COSV66560048;