rs412852

chr1-196734577-G-Achr1-196734577-G-Cchr1-196734577-G-T

Variant summary

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

The NM_000186.4(CFH):c.2414-2247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,814 control chromosomes in the GnomAD database, including 39,778 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 0.71 (39778 hom., cov: 30)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.08

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=-1.22).
• 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.2414-2247G>A		intron_variant		ENST00000367429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000367429.9	c.2414-2247G>A		intron_variant		1	NM_000186.4	P2

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107197 AN: 151694 Hom.: 39721 Cov.: 30

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.707 AC: 107310 AN: 151814 Hom.: 39778 Cov.: 30 AF XY: 0.709 AC XY: 52583 AN XY: 74172

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.711

Alfa AF: 0.480 Hom.: 1197

Bravo AF: 0.735

Asia WGS AF: 0.798 AC: 2776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
Cadd	Benign	0.0030
Dann	Benign	0.38

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: rs412852; hg19: chr1-196703707;