1-196706731-A-G

Position:

• chr1-196706731-A-G

Variant summary

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

The NM_000186.4(CFH):​c.1337-7004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,888 control chromosomes in the GnomAD database, including 11,912 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 0.37 (11912 hom., cov: 31)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFH	NM_000186.4	c.1337-7004A>G		intron_variant		ENST00000367429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000367429.9	c.1337-7004A>G		intron_variant		1	NM_000186.4	P2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56093 AN: 151770 Hom.: 11898 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.370 AC: 56137 AN: 151888 Hom.: 11912 Cov.: 31 AF XY: 0.376 AC XY: 27901 AN XY: 74210

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.381

Alfa AF: 0.377 Hom.: 10719

Bravo AF: 0.381

Asia WGS AF: 0.565 AC: 1961 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.66

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: rs6695321; hg19: chr1-196675861;