Variant chr5-40964714-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000313164.10(C7):c.1750-27C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,599,236 control chromosomes in the GnomAD database, including 46,542 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.27 ( 5590 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40952 hom. )

Consequence

C7
ENST00000313164.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0620

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 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.1750-27C>A		intron_variant		ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10 linkuse as main transcript	c.1750-27C>A		intron_variant		1	NM_000587.4	ENSP00000322061	P1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40272

AN:

151870

Hom.:

5588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.250

AC:

61274

AN:

245016

Hom.:

8237

AF XY:

0.256

AC XY:

33983

AN XY:

132756

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.349

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.233

AC:

336539

AN:

1447248

Hom.:

40952

Cov.:

AF XY:

0.236

AC XY:

170046

AN XY:

720216

show subpopulations

Gnomad4 AFR exome

AF:

0.349

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.231

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.265

AC:

40304

AN:

151988

Hom.:

5590

Cov.:

AF XY:

0.269

AC XY:

19942

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.252

Hom.:

908

Bravo

AF:

0.262

Asia WGS

AF:

0.339

AC:

1178

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.8

DANN

Benign

0.59

BranchPoint Hunter

3.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over