1-196953178-C-T

Position:

• chr1-196953178-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005666.4(CFHR2):​c.430+2150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 152,256 control chromosomes in the GnomAD database, including 1 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 0.0043 (1 hom., cov: 32)
• Consequence: CFHR2 NM_005666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854

Genes affected

CFHR2 (HGNC:4890): (complement factor H related 2) This gene belongs to a family of complement factor H-related genes (CFHR), which are clustered together with complement factor H gene on chromosome 1, and are involved in regulation of complement. Mutations in CFHR genes have been associated with dense deposit disease and atypical haemolytic-uraemic syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR2	NM_005666.4	c.430+2150C>T		intron_variant		ENST00000367415.8	NP_005657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR2	ENST00000367415.8	c.430+2150C>T		intron_variant		1	NM_005666.4	ENSP00000356385	P2

Frequencies

GnomAD3 genomes AF: 0.00435 AC: 662 AN: 152138 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00570

Gnomad OTH AF: 0.00430

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

GnomAD4 genome AF: 0.00435 AC: 662 AN: 152256 Hom.: 1 Cov.: 32 AF XY: 0.00474 AC XY: 353 AN XY: 74440

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.00570

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00479 Hom.: 0

Bravo AF: 0.00354

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.32

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: rs72736421; hg19: chr1-196922308;