6-148212167-T-G

Variant names:

• chr6-148212167-T-G
• rs9377117
• XM_017010599.2:c.45+18542T>G

Variant summary

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

The XM_017010599.2(SASH1):​c.45+18542T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,742 control chromosomes in the GnomAD database, including 5,816 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 0.27 (5816 hom., cov: 32)
• Consequence: SASH1 XM_017010599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40822 AN: 151624 Hom.: 5813 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.269 AC: 40833 AN: 151742 Hom.: 5816 Cov.: 32 AF XY: 0.271 AC XY: 20085 AN XY: 74116

African (AFR) AF: 0.185 AC: 7638 AN: 41378

American (AMR) AF: 0.307 AC: 4682 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 940 AN: 3462

East Asian (EAS) AF: 0.403 AC: 2068 AN: 5134

South Asian (SAS) AF: 0.331 AC: 1589 AN: 4798

European-Finnish (FIN) AF: 0.253 AC: 2649 AN: 10490

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20319 AN: 67912

Other (OTH) AF: 0.269 AC: 568 AN: 2108

Alfa AF: 0.286 Hom.: 10410

Bravo AF: 0.268

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.79
PhyloP100		-0.079

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9377117; hg19: chr6-148533303;