5-41196973-A-G

Position:

• chr5-41196973-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000065.5(C6):​c.446-1040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,892 control chromosomes in the GnomAD database, including 21,904 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 0.53 (21904 hom., cov: 31)
• Consequence: C6 NM_000065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

Genes affected

C6 (HGNC:1339): (complement C6) This gene encodes a component of the complement cascade. The encoded protein is part of the membrane attack complex that can be incorporated into the cell membrane and cause cell lysis. Mutations in this gene are associated with complement component-6 deficiency. Transcript variants encoding the same protein have been described.[provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6	NM_000065.5	c.446-1040T>C		intron_variant		ENST00000337836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6	ENST00000337836.10	c.446-1040T>C		intron_variant		1	NM_000065.5	P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80689 AN: 151774 Hom.: 21909 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.531 AC: 80702 AN: 151892 Hom.: 21904 Cov.: 31 AF XY: 0.530 AC XY: 39385 AN XY: 74258

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.552

Alfa AF: 0.570 Hom.: 22212

Bravo AF: 0.520

Asia WGS AF: 0.502 AC: 1741 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs13168926; hg19: chr5-41197075;