5-40963728-T-C

Variant names:

• chr5-40963728-T-C
• rs324061
• NM_000587.4:c.1750-1013T>C

Variant summary

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

The NM_000587.4(C7):​c.1750-1013T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 151,992 control chromosomes in the GnomAD database, including 46,210 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 0.78 (46210 hom., cov: 30)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.903 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	NM_000587.4	MANE Select	c.1750-1013T>C		intron	N/A	NP_000578.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	ENST00000313164.10	TSL:1 MANE Select	c.1750-1013T>C		intron	N/A	ENSP00000322061.9
	C7	ENST00000908410.1		c.1894-1013T>C		intron	N/A	ENSP00000578469.1
	C7	ENST00000908412.1		c.1750-326T>C		intron	N/A	ENSP00000578471.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118325 AN: 151872 Hom.: 46168 Cov.: 30

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.779 AC: 118428 AN: 151992 Hom.: 46210 Cov.: 30 AF XY: 0.785 AC XY: 58289 AN XY: 74292

African (AFR) AF: 0.811 AC: 33610 AN: 41436

American (AMR) AF: 0.737 AC: 11251 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2966 AN: 3472

East Asian (EAS) AF: 0.925 AC: 4768 AN: 5154

South Asian (SAS) AF: 0.926 AC: 4453 AN: 4808

European-Finnish (FIN) AF: 0.767 AC: 8111 AN: 10570

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50628 AN: 67972

Other (OTH) AF: 0.784 AC: 1656 AN: 2112

Alfa AF: 0.777 Hom.: 11548

Bravo AF: 0.778

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.44
PhyloP100		-0.63
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: rs324061; hg19: chr5-40963830;