Variant rs547154 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000063.6(C2):c.1360+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,612,262 control chromosomes in the GnomAD database, including 8,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1195 hom., cov: 31)

Exomes 𝑓: 0.098 ( 7801 hom. )

Consequence

C2
NM_000063.6 intron

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: -0.537

Variant links:

Genes affected

C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

C2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-31943161-G-T is Benign according to our data. Variant chr6-31943161-G-T is described in ClinVar as [protective]. Clinvar id is 12131.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective]. Variant chr6-31943161-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2	NM_000063.6 linkuse as main transcript	c.1360+62G>T		intron_variant		ENST00000299367.10	NP_000054.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000299367.10 linkuse as main transcript	c.1360+62G>T		intron_variant		1	NM_000063.6	ENSP00000299367	P1	P06681-1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17723

AN:

151974

Hom.:

1197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.0617

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0568

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0908

Gnomad OTH

AF:

0.131

GnomAD4 exome

AF:

0.0982

AC:

143452

AN:

1460170

Hom.:

7801

Cov.:

AF XY:

0.0993

AC XY:

72139

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.0738

Gnomad4 ASJ exome

AF:

0.0555

Gnomad4 EAS exome

AF:

0.0736

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0651

Gnomad4 NFE exome

AF:

0.0950

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.117

AC:

17744

AN:

152092

Hom.:

1195

Cov.:

AF XY:

0.114

AC XY:

8509

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.0571

Gnomad4 EAS

AF:

0.0617

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.0568

Gnomad4 NFE

AF:

0.0908

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0984

Hom.:

602

Bravo

AF:

0.124

Asia WGS

AF:

0.154

AC:

535

AN:

3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Age related macular degeneration 14

Benign:1

protective, no assertion criteria provided

literature only

OMIM

May 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.70

DANN

Benign

0.76

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.

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