Variant 6-148440226-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015278.5(SASH1):c.328C>G(p.Gln110Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00134 in 1,614,052 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q110P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0071 ( 18 hom., cov: 31)

Exomes 𝑓: 0.00074 ( 10 hom. )

Consequence

SASH1
NM_015278.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.43

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008813471).

BP6

Variant 6-148440226-C-G is Benign according to our data. Variant chr6-148440226-C-G is described in ClinVar as [Benign]. Clinvar id is 716141.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00706 (1074/152194) while in subpopulation AFR AF= 0.0245 (1019/41532). AF 95% confidence interval is 0.0233. There are 18 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SASH1	NM_015278.5 linkuse as main transcript	c.328C>G	p.Gln110Glu	missense_variant	3/20	ENST00000367467.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SASH1	ENST00000367467.8 linkuse as main transcript	c.328C>G	p.Gln110Glu	missense_variant	3/20	1	NM_015278.5	P1
SASH1	ENST00000367469.5 linkuse as main transcript	n.246C>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.00708

AC:

1076

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00183

AC:

461

AN:

251432

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0256

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000742

AC:

1085

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000667

AC XY:

485

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0260

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00706

AC:

1074

AN:

152194

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

536

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0245

Gnomad4 AMR

AF:

0.00282

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.00817

ESP6500AA

AF:

0.0236

AC:

104

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00227

AC:

275

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Benign

0.88

DEOGEN2

Benign

0.014

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.27

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.37

REVEL

Benign

0.19

Sift

Benign

0.22

Sift4G

Benign

1.0

Polyphen

0.98

Vest4

0.72

MVP

0.59

MPC

0.21

ClinPred

0.033

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.085

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over