rs6570847

Variant names:

• chr6-148363727-C-G
• rs6570847
• NM_015278.5:c.156+20504C>G

Variant summary

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

The NM_015278.5(SASH1):​c.156+20504C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 151,600 control chromosomes in the GnomAD database, including 44,764 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 0.77 (44764 hom., cov: 28)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASH1	NM_015278.5	c.156+20504C>G		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.156+20504C>G		intron_variant	Intron 1 of 19	1	NM_015278.5	ENSP00000356437.3
SASH1	ENST00000367469.5	n.75-26407C>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.765 AC: 115922 AN: 151482 Hom.: 44723 Cov.: 28

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.765 AC: 116016 AN: 151600 Hom.: 44764 Cov.: 28 AF XY: 0.765 AC XY: 56680 AN XY: 74046

African (AFR) AF: 0.851 AC: 35195 AN: 41334

American (AMR) AF: 0.832 AC: 12641 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2674 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3031 AN: 5128

South Asian (SAS) AF: 0.831 AC: 3986 AN: 4794

European-Finnish (FIN) AF: 0.701 AC: 7346 AN: 10486

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48608 AN: 67886

Other (OTH) AF: 0.753 AC: 1578 AN: 2096

Alfa AF: 0.733 Hom.: 5094

Bravo AF: 0.777

Asia WGS AF: 0.681 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.72
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: rs6570847; hg19: chr6-148684863;