1-196677046-T-G

Position:

• chr1-196677046-T-G

Variant summary

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

The ENST00000367429.9(CFH):​c.428-430T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 160,712 control chromosomes in the GnomAD database, including 35,672 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 (33757 hom., cov: 32)
  • Exomes 𝑓: 0.64 (1915 hom.)
• Consequence: CFH ENST00000367429.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848

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=-0.98).
• 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.428-430T>G		intron_variant		ENST00000367429.9	NP_000177.2
CFH	NM_001014975.3	c.428-430T>G		intron_variant			NP_001014975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.428-430T>G		intron_variant		1	NM_000186.4	ENSP00000356399	P2

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100493 AN: 151794 Hom.: 33731 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.678

GnomAD4 exome AF: 0.642 AC: 5649 AN: 8800 Hom.: 1915 Cov.: 0 AF XY: 0.632 AC XY: 2985 AN XY: 4722

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.947

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.505

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.662 AC: 100565 AN: 151912 Hom.: 33757 Cov.: 32 AF XY: 0.665 AC XY: 49372 AN XY: 74220

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.677

Alfa AF: 0.618 Hom.: 51839

Bravo AF: 0.680

Asia WGS AF: 0.782 AC: 2710 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.39
DANN	Benign	0.23

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: rs1329424; hg19: chr1-196646176;