1-196677257-T-C

Position:

• chr1-196677257-T-C

Variant summary

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

The ENST00000367429.9(CFH):​c.428-219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 474,706 control chromosomes in the GnomAD database, including 17,796 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 0.22 (4507 hom., cov: 32)
  • Exomes 𝑓: 0.27 (13289 hom.)
• Consequence: CFH ENST00000367429.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFH	NM_000186.4	c.428-219T>C		intron_variant		ENST00000367429.9	NP_000177.2
CFH	NM_001014975.3	c.428-219T>C		intron_variant			NP_001014975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.428-219T>C		intron_variant		1	NM_000186.4	ENSP00000356399	P2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33655 AN: 151852 Hom.: 4504 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.271 AC: 87372 AN: 322736 Hom.: 13289 Cov.: 3 AF XY: 0.269 AC XY: 45564 AN XY: 169352

Gnomad4 AFR exome AF: 0.0960

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.221 AC: 33655 AN: 151970 Hom.: 4507 Cov.: 32 AF XY: 0.220 AC XY: 16365 AN XY: 74286

Gnomad4 AFR AF: 0.0980

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.230

Alfa AF: 0.247 Hom.: 1020

Bravo AF: 0.229

Asia WGS AF: 0.291 AC: 1012 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.8
DANN	Benign	0.80

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: rs1329423; hg19: chr1-196646387;