chr5-41231711-G-A

Position:

• chr5-41231711-G-A

Variant summary

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

The ENST00000263413.7(C6):​c.-20-28461C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,638 control chromosomes in the GnomAD database, including 25,320 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 0.56 (25320 hom., cov: 31)
• Consequence: C6 ENST00000263413.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C6	NM_001115131.4	c.-20-28461C>T		intron_variant			NP_001108603.2
C6	XM_006714496.5	c.8-28461C>T		intron_variant			XP_006714559.1
C6	XM_011514114.4	c.8-28461C>T		intron_variant			XP_011512416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000263413.7	c.-20-28461C>T		intron_variant		1		ENSP00000263413	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 84937 AN: 151520 Hom.: 25318 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.560 AC: 84952 AN: 151638 Hom.: 25320 Cov.: 31 AF XY: 0.562 AC XY: 41597 AN XY: 74050

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.580

Alfa AF: 0.641 Hom.: 57609

Bravo AF: 0.543

Asia WGS AF: 0.586 AC: 2018 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4957381; hg19: chr5-41231813;