6-148343268-G-A

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.156+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,530,962 control chromosomes in the GnomAD database, including 10,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (745 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9866 hom.)
• Consequence: SASH1 NM_015278.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.419

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=-0.8).
• BP6: Variant 6-148343268-G-A is Benign according to our data. Variant chr6-148343268-G-A is described in ClinVar as [Benign]. Clinvar id is 1251256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SASH1	NM_015278.5	c.156+45G>A		intron_variant		ENST00000367467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SASH1	ENST00000367467.8	c.156+45G>A		intron_variant		1	NM_015278.5	P1
SASH1	ENST00000367469.5	n.75-46866G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12886 AN: 152118 Hom.: 745 Cov.: 32

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0865

GnomAD3 exomes AF: 0.0932 AC: 19023 AN: 204200 Hom.: 1124 AF XY: 0.0984 AC XY: 11145 AN XY: 113258

Gnomad AFR exome AF: 0.0236

Gnomad AMR exome AF: 0.0388

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.000289

Gnomad SAS exome AF: 0.0917

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.0977

GnomAD4 exome AF: 0.115 AC: 158847 AN: 1378726 Hom.: 9866 Cov.: 27 AF XY: 0.115 AC XY: 78700 AN XY: 681938

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.0435

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.000256

Gnomad4 SAS exome AF: 0.0921

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.0981

GnomAD4 genome AF: 0.0846 AC: 12886 AN: 152236 Hom.: 745 Cov.: 32 AF XY: 0.0830 AC XY: 6175 AN XY: 74438

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.104 Hom.: 274

Bravo AF: 0.0764

Asia WGS AF: 0.0530 AC: 183 AN: 3478

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

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.8
Dann	Benign	0.78

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: rs55914407; hg19: chr6-148664404;