rs12527089

chr6-148466023-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015278.5(SASH1):c.387-2522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 152,170 control chromosomes in the GnomAD database, including 248 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 0.046 (248 hom., cov: 32)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SASH1	NM_015278.5	c.387-2522C>T		intron_variant		ENST00000367467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SASH1	ENST00000367467.8	c.387-2522C>T		intron_variant		1	NM_015278.5	P1
SASH1	ENST00000637469.1	c.32-2522C>T		intron_variant, NMD_transcript_variant		4
SASH1	ENST00000470750.1	n.51-2522C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7052 AN: 152052 Hom.: 249 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0463 AC: 7052 AN: 152170 Hom.: 248 Cov.: 32 AF XY: 0.0507 AC XY: 3774 AN XY: 74374

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.0999

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0514 Hom.: 322

Bravo AF: 0.0444

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.2
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs12527089; hg19: chr6-148787159;