1-196727745-G-T

Position:

• chr1-196727745-G-T

Variant summary

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

The NM_000186.4(CFH):​c.2237-601G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,214 control chromosomes in the GnomAD database, including 64,886 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 0.92 (64886 hom., cov: 32)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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]

ENSG00000289697 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFH	NM_000186.4	c.2237-601G>T		intron_variant		ENST00000367429.9	NP_000177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.2237-601G>T		intron_variant		1	NM_000186.4	ENSP00000356399.4
ENSG00000289697	ENST00000696032.1	c.2237-601G>T		intron_variant				ENSP00000512341.1

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140219 AN: 152096 Hom.: 64829 Cov.: 32

Gnomad AFR AF: 0.979

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.923

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

GnomAD4 genome AF: 0.922 AC: 140333 AN: 152214 Hom.: 64886 Cov.: 32 AF XY: 0.924 AC XY: 68783 AN XY: 74402

Gnomad4 AFR AF: 0.979

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.902

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.924

Alfa AF: 0.884 Hom.: 56859

Bravo AF: 0.929

Asia WGS AF: 0.969 AC: 3368 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.081
DANN	Benign	0.49

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: rs419137; hg19: chr1-196696875;