6-148466870-C-T

Variant names:

• chr6-148466870-C-T
• rs6930337
• NM_015278.5:c.387-1675C>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.387-1675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 151,934 control chromosomes in the GnomAD database, including 2,030 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 0.13 (2030 hom., cov: 31)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASH1	NM_015278.5	c.387-1675C>T		intron_variant	Intron 4 of 19	ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SASH1	ENST00000367467.8	c.387-1675C>T		intron_variant	Intron 4 of 19	1	NM_015278.5	ENSP00000356437.3
SASH1	ENST00000470750.1	n.51-1675C>T		intron_variant	Intron 1 of 1	3
SASH1	ENST00000637469.1	n.30-1675C>T		intron_variant	Intron 1 of 4	4		ENSP00000490499.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19880 AN: 151816 Hom.: 2021 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0987

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

GnomAD4 genome AF: 0.131 AC: 19912 AN: 151934 Hom.: 2030 Cov.: 31 AF XY: 0.133 AC XY: 9841 AN XY: 74268

African (AFR) AF: 0.275 AC: 11376 AN: 41386

American (AMR) AF: 0.132 AC: 2011 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3468

East Asian (EAS) AF: 0.0206 AC: 106 AN: 5136

South Asian (SAS) AF: 0.178 AC: 854 AN: 4798

European-Finnish (FIN) AF: 0.0686 AC: 726 AN: 10578

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4333 AN: 67972

Other (OTH) AF: 0.0972 AC: 205 AN: 2110

Alfa AF: 0.0932 Hom.: 2357

Bravo AF: 0.138

Asia WGS AF: 0.141 AC: 490 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	0.90
DANN	Benign	0.36
PhyloP100		-0.94
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: rs6930337; hg19: chr6-148788006;