Variant 5-40949895-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000587.4(C7):c.983-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,501,092 control chromosomes in the GnomAD database, including 309,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33663 hom., cov: 31)

Exomes 𝑓: 0.64 ( 275474 hom. )

Consequence

C7
NM_000587.4 intron

Scores

Splicing: ADA: 0.00001686

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.512

Variant links:

Genes affected

C7 (HGNC:1346): (complement C7) This gene encodes a serum glycoprotein that forms a membrane attack complex together with complement components C5b, C6, C8, and C9 as part of the terminal complement pathway of the innate immune system. The protein encoded by this gene contains a cholesterol-dependent cytolysin/membrane attack complex/perforin-like (CDC/MACPF) domain and belongs to a large family of structurally related molecules that form pores involved in host immunity and bacterial pathogenesis. This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. Mutations in this gene are associated with a rare disorder called C7 deficiency. [provided by RefSeq, Nov 2016]

C7 links:

C7 (HGNC:):

C7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-40949895-C-T is Benign according to our data. Variant chr5-40949895-C-T is described in ClinVar as [Benign]. Clinvar id is 1170113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-40949895-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7	NM_000587.4 linkuse as main transcript	c.983-9C>T		intron_variant		ENST00000313164.10	NP_000578.2	P10643Q05CI3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10 linkuse as main transcript	c.983-9C>T		intron_variant		1	NM_000587.4	ENSP00000322061.9		P10643

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

100905

AN:

151838

Hom.:

33640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.682

Gnomad SAS

AF:

0.609

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.653

GnomAD3 exomes

AF:

0.644

AC:

121860

AN:

189342

Hom.:

39387

AF XY:

0.642

AC XY:

64381

AN XY:

100336

show subpopulations

Gnomad AFR exome

AF:

0.735

Gnomad AMR exome

AF:

0.608

Gnomad ASJ exome

AF:

0.675

Gnomad EAS exome

AF:

0.703

Gnomad SAS exome

AF:

0.602

Gnomad FIN exome

AF:

0.672

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.641

GnomAD4 exome

AF:

0.638

AC:

860346

AN:

1349136

Hom.:

275474

Cov.:

AF XY:

0.636

AC XY:

427226

AN XY:

671244

show subpopulations

Gnomad4 AFR exome

AF:

0.736

Gnomad4 AMR exome

AF:

0.610

Gnomad4 ASJ exome

AF:

0.667

Gnomad4 EAS exome

AF:

0.655

Gnomad4 SAS exome

AF:

0.607

Gnomad4 FIN exome

AF:

0.678

Gnomad4 NFE exome

AF:

0.634

Gnomad4 OTH exome

AF:

0.646

GnomAD4 genome

AF:

0.665

AC:

100977

AN:

151956

Hom.:

33663

Cov.:

AF XY:

0.665

AC XY:

49398

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.732

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.672

Gnomad4 EAS

AF:

0.682

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.689

Gnomad4 NFE

AF:

0.632

Gnomad4 OTH

AF:

0.656

Alfa

AF:

0.639

Hom.:

36902

Bravo

AF:

0.661

Asia WGS

AF:

0.645

AC:

2244

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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

-0.90

CADD

Benign

0.21

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0

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