rs6930576

Variant names:

• chr6-148383818-G-A
• rs6930576
• NM_015278.5:c.157-6316G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-148383818-G-A
• chr6-148383818-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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]

SASH1 Gene-Disease associations (from GenCC):

• dyschromatosis universalis hereditaria 1

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• familial generalized lentiginosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SASH1	NM_015278.5	c.157-6316G>A		intron_variant	Intron 1 of 19	ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SASH1	ENST00000367467.8	c.157-6316G>A		intron_variant	Intron 1 of 19	1	NM_015278.5	ENSP00000356437.3
SASH1	ENST00000367469.5	n.75-6316G>A		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.305 AC: 12654 AN: 41452

American (AMR) AF: 0.413 AC: 6295 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1577 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1017 AN: 5172

South Asian (SAS) AF: 0.389 AC: 1872 AN: 4816

European-Finnish (FIN) AF: 0.291 AC: 3077 AN: 10560

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26411 AN: 67942

Other (OTH) AF: 0.383 AC: 806 AN: 2106

Alfa AF: 0.375 Hom.: 35157

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
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6930576; hg19: chr6-148704954;