dbSNP rs1124163: SASH1:c.627+6361C>T (chr6-148480583-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015278.5(SASH1):c.627+6361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,994 control chromosomes in the GnomAD database, including 2,993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2993 hom., cov: 31)

Exomes 𝑓: 0.15 ( 0 hom. )

Consequence

SASH1
NM_015278.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.458

Publications

1 publications found

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:

CYP51A1P3 (HGNC:41991): (cytochrome P450 family 51 subfamily A member 1 pseudogene 3)

CYP51A1P3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASH1	NM_015278.5 link	c.627+6361C>T		intron_variant	Intron 7 of 19	ENST00000367467.8	NP_056093.3	O94885

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SASH1	ENST00000367467.8 link	c.627+6361C>T	intron_variant	Intron 7 of 19	1	NM_015278.5	ENSP00000356437.3	O94885
CYP51A1P3	ENST00000400072.3 link	n.1248C>T	non_coding_transcript_exon_variant	Exon 3 of 3	6
SASH1	ENST00000637469.1 link	n.71-7031C>T	intron_variant	Intron 2 of 4	4		ENSP00000490499.1	A0A1B0GVF9

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26888

AN:

151806

Hom.:

2984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.171

GnomAD4 exome

AF:

0.147

AC:

AN:

Hom.:

Cov.:

AF XY:

0.132

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.208

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.177

AC:

26904

AN:

151926

Hom.:

2993

Cov.:

AF XY:

0.176

AC XY:

13086

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.318

AC:

13182

AN:

41390

American (AMR)

AF:

0.104

AC:

1586

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

498

AN:

3466

East Asian (EAS)

AF:

0.120

AC:

618

AN:

5166

South Asian (SAS)

AF:

0.212

AC:

1019

AN:

4810

European-Finnish (FIN)

AF:

0.135

AC:

1424

AN:

10572

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8014

AN:

67944

Other (OTH)

AF:

0.170

AC:

359

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1079

2158

3237

4316

5395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.136

Hom.:

922

Bravo

AF:

0.180

Asia WGS

AF:

0.193

AC:

669

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.57

(source)

DANN

Benign

0.61

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over