rs742855

chr1-196736390-T-C

Variant summary

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

The NM_000186.4(CFH):c.2414-434T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,014 control chromosomes in the GnomAD database, including 2,517 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 0.16 (2517 hom., cov: 32)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFH	NM_000186.4	c.2414-434T>C		intron_variant		ENST00000367429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000367429.9	c.2414-434T>C		intron_variant		1	NM_000186.4	P2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24671 AN: 151896 Hom.: 2517 Cov.: 32

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.162 AC: 24676 AN: 152014 Hom.: 2517 Cov.: 32 AF XY: 0.163 AC XY: 12129 AN XY: 74288

Gnomad4 AFR AF: 0.0936

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.161

Alfa AF: 0.177 Hom.: 2358

Bravo AF: 0.172

Asia WGS AF: 0.239 AC: 829 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.34
Dann	Benign	0.54

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: rs742855; hg19: chr1-196705520;