chr6-148343268-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.419
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]

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ACMG classification

Classification made for transcript

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
SASH1NM_015278.5 linkuse as main transcriptc.156+45G>A intron_variant ENST00000367467.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SASH1ENST00000367467.8 linkuse as main transcriptc.156+45G>A intron_variant 1 NM_015278.5 P1
SASH1ENST00000367469.5 linkuse as main transcriptn.75-46866G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0847
AC:
12886
AN:
152118
Hom.:
745
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 15, 2021- -

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

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

Other links and lift over

dbSNP: rs55914407; hg19: chr6-148664404; API