Variant 8-144103543-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_030974.4(SHARPIN):c.201+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,531,116 control chromosomes in the GnomAD database, including 637,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 57715 hom., cov: 35)

Exomes 𝑓: 0.92 ( 579568 hom. )

Consequence

SHARPIN
NM_030974.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.165

Variant links:

Genes affected

SHARPIN (HGNC:25321): (SHANK associated RH domain interactor) Enables polyubiquitin modification-dependent protein binding activity. Involved in protein linear polyubiquitination and regulation of signal transduction. Located in cytosol. Part of LUBAC complex. [provided by Alliance of Genome Resources, Apr 2022]

SHARPIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 8-144103543-C-T is Benign according to our data. Variant chr8-144103543-C-T is described in ClinVar as [Benign]. Clinvar id is 403433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHARPIN	NM_030974.4 link	c.201+10G>A		intron_variant	Intron 1 of 8	ENST00000398712.7	NP_112236.3	Q9H0F6-1Q6PJD5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHARPIN	ENST00000398712.7 link	c.201+10G>A		intron_variant	Intron 1 of 8	1	NM_030974.4	ENSP00000381698.2		Q9H0F6-1

Frequencies

GnomAD3 genomes

AF:

0.865

AC:

131596

AN:

152136

Hom.:

57694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.944

Gnomad AMR

AF:

0.913

Gnomad ASJ

AF:

0.922

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.959

Gnomad FIN

AF:

0.928

Gnomad MID

AF:

0.882

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.878

GnomAD3 exomes

AF:

0.926

AC:

116966

AN:

126264

Hom.:

54369

AF XY:

0.929

AC XY:

64244

AN XY:

69122

show subpopulations

Gnomad AFR exome

AF:

0.713

Gnomad AMR exome

AF:

0.944

Gnomad ASJ exome

AF:

0.925

Gnomad EAS exome

AF:

0.995

Gnomad SAS exome

AF:

0.961

Gnomad FIN exome

AF:

0.919

Gnomad NFE exome

AF:

0.914

Gnomad OTH exome

AF:

0.925

GnomAD4 exome

AF:

0.916

AC:

1262979

AN:

1378866

Hom.:

579568

Cov.:

AF XY:

0.918

AC XY:

624576

AN XY:

680234

show subpopulations

Gnomad4 AFR exome

AF:

0.698

Gnomad4 AMR exome

AF:

0.941

Gnomad4 ASJ exome

AF:

0.926

Gnomad4 EAS exome

AF:

0.996

Gnomad4 SAS exome

AF:

0.960

Gnomad4 FIN exome

AF:

0.924

Gnomad4 NFE exome

AF:

0.915

Gnomad4 OTH exome

AF:

0.911

GnomAD4 genome

AF:

0.865

AC:

131670

AN:

152250

Hom.:

57715

Cov.:

AF XY:

0.869

AC XY:

64661

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.710

Gnomad4 AMR

AF:

0.913

Gnomad4 ASJ

AF:

0.922

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.958

Gnomad4 FIN

AF:

0.928

Gnomad4 NFE

AF:

0.918

Gnomad4 OTH

AF:

0.879

Alfa

AF:

0.904

Hom.:

6799

Bravo

AF:

0.856

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.8

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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