5-40960521-A-T

Variant names:

• chr5-40960521-A-T
• rs3805215
• NM_000587.4:c.1661+901A>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.1661+901A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,956 control chromosomes in the GnomAD database, including 3,241 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 0.19 (3241 hom., cov: 31)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C7	NM_000587.4	c.1661+901A>T		intron_variant	Intron 12 of 17	ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10	c.1661+901A>T		intron_variant	Intron 12 of 17	1	NM_000587.4	ENSP00000322061.9

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28278 AN: 151838 Hom.: 3240 Cov.: 31

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.186 AC: 28283 AN: 151956 Hom.: 3241 Cov.: 31 AF XY: 0.193 AC XY: 14316 AN XY: 74278

African (AFR) AF: 0.0622 AC: 2579 AN: 41460

American (AMR) AF: 0.165 AC: 2520 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3462

East Asian (EAS) AF: 0.377 AC: 1939 AN: 5148

South Asian (SAS) AF: 0.343 AC: 1654 AN: 4818

European-Finnish (FIN) AF: 0.236 AC: 2493 AN: 10554

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15349 AN: 67938

Other (OTH) AF: 0.212 AC: 447 AN: 2104

Alfa AF: 0.202 Hom.: 418

Bravo AF: 0.172

Asia WGS AF: 0.332 AC: 1149 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		-0.48
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: rs3805215; hg19: chr5-40960623;