rs6860438

Variant names:

• chr5-40979560-G-T
• rs6860438
• NM_000587.4:c.2166-165G>T

Variant summary

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

The NM_000587.4(C7):​c.2166-165G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,346 control chromosomes in the GnomAD database, including 13,228 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 0.42 (13228 hom., cov: 30)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 5 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: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 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.2166-165G>T		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.2166-165G>T		intron	N/A	ENSP00000322061.9	P10643
	C7	ENST00000908410.1		c.2310-165G>T		intron	N/A	ENSP00000578469.1
	C7	ENST00000908412.1		c.2256-165G>T		intron	N/A	ENSP00000578471.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63309 AN: 151244 Hom.: 13214 Cov.: 30

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.419 AC: 63359 AN: 151346 Hom.: 13228 Cov.: 30 AF XY: 0.418 AC XY: 30882 AN XY: 73844

African (AFR) AF: 0.429 AC: 17718 AN: 41254

American (AMR) AF: 0.377 AC: 5743 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1340 AN: 3462

East Asian (EAS) AF: 0.312 AC: 1601 AN: 5136

South Asian (SAS) AF: 0.509 AC: 2445 AN: 4804

European-Finnish (FIN) AF: 0.439 AC: 4509 AN: 10278

Middle Eastern (MID) AF: 0.340 AC: 98 AN: 288

European-Non Finnish (NFE) AF: 0.423 AC: 28749 AN: 67902

Other (OTH) AF: 0.402 AC: 842 AN: 2096

Alfa AF: 0.421 Hom.: 3970

Bravo AF: 0.412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.072
DANN	Benign	0.22
PhyloP100		-1.3
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: rs6860438; hg19: chr5-40979662;