rs6876739

Variant names:

• chr5-40938240-T-C
• rs6876739
• NM_000587.4:c.567+550T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-40938240-T-C
• chr5-40938240-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000587.4(C7):​c.567+550T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,986 control chromosomes in the GnomAD database, including 18,432 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 0.48 (18432 hom., cov: 31)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• complement component 7 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000587.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	NM_000587.4	MANE Select	c.567+550T>C		intron	N/A	NP_000578.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	ENST00000313164.10	TSL:1 MANE Select	c.567+550T>C		intron	N/A	ENSP00000322061.9
	C7	ENST00000696333.1		c.567+550T>C		intron	N/A	ENSP00000512566.1
	C7	ENST00000696441.1		c.567+550T>C		intron	N/A	ENSP00000512631.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72820 AN: 151866 Hom.: 18406 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.480 AC: 72895 AN: 151986 Hom.: 18432 Cov.: 31 AF XY: 0.477 AC XY: 35413 AN XY: 74266

African (AFR) AF: 0.664 AC: 27552 AN: 41470

American (AMR) AF: 0.443 AC: 6760 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2417 AN: 5152

South Asian (SAS) AF: 0.463 AC: 2230 AN: 4820

European-Finnish (FIN) AF: 0.382 AC: 4030 AN: 10544

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27240 AN: 67968

Other (OTH) AF: 0.451 AC: 951 AN: 2110

Alfa AF: 0.457 Hom.: 2778

Bravo AF: 0.494

Asia WGS AF: 0.493 AC: 1714 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.6
DANN	Benign	0.65
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6876739; hg19: chr5-40938342;