chr6-148371999-C-A

Variant names:

• chr6-148371999-C-A
• rs17712470
• NM_015278.5:c.157-18135C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015278.5(SASH1):​c.157-18135C>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
• Publications: 4 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=-0.91).
• 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 rank	MANE	Protein	UniProt
SASH1	NM_015278.5	c.157-18135C>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.157-18135C>A		intron_variant	Intron 1 of 19	1	NM_015278.5	ENSP00000356437.3
SASH1	ENST00000367469.5	n.75-18135C>A		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.191 AC: 7907 AN: 41372

American (AMR) AF: 0.227 AC: 3462 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3472

East Asian (EAS) AF: 0.141 AC: 729 AN: 5172

South Asian (SAS) AF: 0.234 AC: 1125 AN: 4806

European-Finnish (FIN) AF: 0.341 AC: 3599 AN: 10542

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20844 AN: 67966

Other (OTH) AF: 0.252 AC: 533 AN: 2114

Alfa AF: 0.190 Hom.: 540

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
PhyloP100		-0.54
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: rs17712470; hg19: chr6-148693135;