chr6-148439903-G-T

Position:

• chr6-148439903-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015278.5(SASH1):​c.286-281G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,046 control chromosomes in the GnomAD database, including 13,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (13772 hom., cov: 32)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.609

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-148439903-G-T is Benign according to our data. Variant chr6-148439903-G-T is described in ClinVar as [Benign]. Clinvar id is 1288999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SASH1	NM_015278.5	c.286-281G>T		intron_variant		ENST00000367467.8	NP_056093.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SASH1	ENST00000367467.8	c.286-281G>T		intron_variant		1	NM_015278.5	ENSP00000356437	P1
SASH1	ENST00000367469.5	n.204-281G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64089 AN: 151928 Hom.: 13765 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.422 AC: 64126 AN: 152046 Hom.: 13772 Cov.: 32 AF XY: 0.430 AC XY: 31931 AN XY: 74324

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.393

Alfa AF: 0.494 Hom.: 1893

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.52

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: rs10872615; hg19: chr6-148761039;