rs393955

Positions:

• chr1-196723340-C-A
• chr1-196723340-C-G

Variant summary

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

The NM_000186.4(CFH):​c.1697-1781C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,956 control chromosomes in the GnomAD database, including 33,394 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 0.66 (33394 hom., cov: 31)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-0.89).
• 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	Protein	UniProt
CFH	NM_000186.4	c.1697-1781C>A		intron_variant		ENST00000367429.9	NP_000177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.1697-1781C>A		intron_variant		1	NM_000186.4	ENSP00000356399	P2

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99487 AN: 151838 Hom.: 33356 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.655 AC: 99577 AN: 151956 Hom.: 33394 Cov.: 31 AF XY: 0.660 AC XY: 49002 AN XY: 74236

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.674

Alfa AF: 0.546 Hom.: 14245

Bravo AF: 0.676

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
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: rs393955; hg19: chr1-196692470;