rs1147857

Variant names:

• chr6-148520616-T-C
• rs1147857
• NM_015278.5:c.1209+723T>C

Variant summary

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

The NM_015278.5(SASH1):​c.1209+723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,882 control chromosomes in the GnomAD database, including 16,680 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 0.45 (16680 hom., cov: 31)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASH1	NM_015278.5	c.1209+723T>C		intron_variant	Intron 10 of 19	ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SASH1	ENST00000367467.8	c.1209+723T>C		intron_variant	Intron 10 of 19	1	NM_015278.5	ENSP00000356437.3
SASH1	ENST00000636279.1	c.969+234T>C		intron_variant	Intron 2 of 3	5		ENSP00000490865.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69042 AN: 151762 Hom.: 16683 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.455 AC: 69055 AN: 151882 Hom.: 16680 Cov.: 31 AF XY: 0.458 AC XY: 33956 AN XY: 74218

African (AFR) AF: 0.281 AC: 11634 AN: 41422

American (AMR) AF: 0.490 AC: 7484 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3464

East Asian (EAS) AF: 0.687 AC: 3537 AN: 5146

South Asian (SAS) AF: 0.481 AC: 2313 AN: 4806

European-Finnish (FIN) AF: 0.580 AC: 6111 AN: 10528

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34981 AN: 67934

Other (OTH) AF: 0.478 AC: 1006 AN: 2106

Alfa AF: 0.504 Hom.: 53129

Bravo AF: 0.440

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		-0.86
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: rs1147857; hg19: chr6-148841752;