rs12029785

Positions:

• chr1-196689775-G-A
• chr1-196689775-G-C
• chr1-196689775-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000367429.9(CFH):​c.1159+161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,830 control chromosomes in the GnomAD database, including 32,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.65 (32031 hom., cov: 32)
• Consequence: CFH ENST00000367429.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.290

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-196689775-G-A is Benign according to our data. Variant chr1-196689775-G-A is described in ClinVar as [Benign]. Clinvar id is 1289573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.1159+161G>A		intron_variant		ENST00000367429.9	NP_000177.2
CFH	NM_001014975.3	c.1159+161G>A		intron_variant			NP_001014975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.1159+161G>A		intron_variant		1	NM_000186.4	ENSP00000356399	P2

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97868 AN: 151712 Hom.: 32007 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.645 AC: 97933 AN: 151830 Hom.: 32031 Cov.: 32 AF XY: 0.648 AC XY: 48091 AN XY: 74194

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.664

Alfa AF: 0.526 Hom.: 1606

Bravo AF: 0.661

Asia WGS AF: 0.780 AC: 2710 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.54
DANN	Benign	0.16

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: rs12029785; hg19: chr1-196658905;