1-196751925-T-C

Position:

• chr1-196751925-T-C

Variant summary

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

The ENST00000696032.1(ENSG00000289697):​c.3580+4728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 146,710 control chromosomes in the GnomAD database, including 227 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 0.20 (227 hom., cov: 30)
• Consequence: ENSG00000289697 ENST00000696032.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.78

Genes affected

ENSG00000289697 (HGNC:):

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.196751925T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289697	ENST00000696032.1	c.3580+4728T>C		intron_variant				ENSP00000512341.1
CFH	ENST00000695981.1	c.3581-147T>C		intron_variant				ENSP00000512306.1
ENSG00000289697	ENST00000696033.1	c.1160-27872T>C		intron_variant				ENSP00000512342.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 28780 AN: 146600 Hom.: 224 Cov.: 30

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.196 AC: 28802 AN: 146710 Hom.: 227 Cov.: 30 AF XY: 0.194 AC XY: 13898 AN XY: 71682

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.185

Alfa AF: 0.190 Hom.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1066420; hg19: chr1-196721055;