rs203685

chr1-196708815-C-Achr1-196708815-C-Gchr1-196708815-C-T

Variant summary

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

The NM_000186.4(CFH):c.1337-4920C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,924 control chromosomes in the GnomAD database, including 34,807 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 0.67 (34807 hom., cov: 31)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

Genes affected

CFH (HGNC:4883): (complement factor H) This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFH	NM_000186.4	c.1337-4920C>A		intron_variant		ENST00000367429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000367429.9	c.1337-4920C>A		intron_variant		1	NM_000186.4	P2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101361 AN: 151808 Hom.: 34768 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.668 AC: 101452 AN: 151924 Hom.: 34807 Cov.: 31 AF XY: 0.672 AC XY: 49888 AN XY: 74226

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.684

Alfa AF: 0.597 Hom.: 22675

Bravo AF: 0.690

Asia WGS AF: 0.787 AC: 2735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.031
Dann	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs203685; hg19: chr1-196677945;