1-196705787-T-C

Position:

• chr1-196705787-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.1337-7948T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,930 control chromosomes in the GnomAD database, including 30,148 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 0.62 (30148 hom., cov: 31)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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=-0.99).
• 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.1337-7948T>C		intron_variant		ENST00000367429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000367429.9	c.1337-7948T>C		intron_variant		1	NM_000186.4	P2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94738 AN: 151812 Hom.: 30126 Cov.: 31

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.624 AC: 94803 AN: 151930 Hom.: 30148 Cov.: 31 AF XY: 0.629 AC XY: 46729 AN XY: 74236

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.646

Alfa AF: 0.596 Hom.: 12975

Bravo AF: 0.641

Asia WGS AF: 0.774 AC: 2689 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.58

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: rs2019724; hg19: chr1-196674917;