1-196727803-G-A

Position:

• chr1-196727803-G-A

Variant summary

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

The NM_000186.4(CFH):​c.2237-543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,002 control chromosomes in the GnomAD database, including 16,344 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 0.46 (16344 hom., cov: 33)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFH	NM_000186.4	c.2237-543G>A		intron_variant		ENST00000367429.9	NP_000177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.2237-543G>A		intron_variant		1	NM_000186.4	ENSP00000356399	P2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69713 AN: 151884 Hom.: 16321 Cov.: 33

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.459 AC: 69778 AN: 152002 Hom.: 16344 Cov.: 33 AF XY: 0.464 AC XY: 34477 AN XY: 74312

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.481

Alfa AF: 0.403 Hom.: 25050

Bravo AF: 0.466

Asia WGS AF: 0.532 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.43

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: rs1410996; hg19: chr1-196696933;