rs55914407

Variant names:

• chr6-148343268-G-A
• rs55914407
• NM_015278.5:c.156+45G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-148343268-G-A
• chr6-148343268-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: PanelApp Australia, 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, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015278.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SASH1	NM_015278.5	MANE Select	c.156+45G>A		intron	N/A	NP_056093.3
	SASH1	NM_001346505.2		c.22-46866G>A		intron	N/A	NP_001333434.1
	SASH1	NM_001346506.2		c.-282+45G>A		intron	N/A	NP_001333435.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SASH1	ENST00000367467.8	TSL:1 MANE Select	c.156+45G>A		intron	N/A	ENSP00000356437.3	O94885
	SASH1	ENST00000946242.1		c.156+45G>A		intron	N/A	ENSP00000616301.1
	SASH1	ENST00000946243.1		c.156+45G>A		intron	N/A	ENSP00000616302.1

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

GnomAD2 exomes AF: 0.0932 AC: 19023 AN: 204200 AF XY: 0.0984

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 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

African (AFR) AF: 0.0193 AC: 581 AN: 30084

American (AMR) AF: 0.0435 AC: 1764 AN: 40596

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2696 AN: 24296

East Asian (EAS) AF: 0.000256 AC: 9 AN: 35128

South Asian (SAS) AF: 0.0921 AC: 7433 AN: 80666

European-Finnish (FIN) AF: 0.124 AC: 4687 AN: 37710

Middle Eastern (MID) AF: 0.0847 AC: 470 AN: 5552

European-Non Finnish (NFE) AF: 0.127 AC: 135638 AN: 1067904

Other (OTH) AF: 0.0981 AC: 5569 AN: 56790

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

African (AFR) AF: 0.0232 AC: 965 AN: 41564

American (AMR) AF: 0.0562 AC: 860 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0895 AC: 432 AN: 4826

European-Finnish (FIN) AF: 0.120 AC: 1273 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8717 AN: 67982

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.104 Hom.: 274

Bravo AF: 0.0764

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.78
PhyloP100		0.42
PromoterAI		0.019	Neutral
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: rs55914407; hg19: chr6-148664404;