1-196977290-T-A

Position:

• chr1-196977290-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000699466.1(CFHR5):​c.-198+2176T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 139,436 control chromosomes in the GnomAD database, including 4,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (4256 hom., cov: 29)
• Consequence: CFHR5 ENST00000699466.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.531

Genes affected

CFHR5 (HGNC:24668): (complement factor H related 5) This gene is a member of a small complement factor H (CFH) gene cluster on chromosome 1. Each member of this gene family contains multiple short consensus repeats (SCRs) typical of regulators of complement activation. The protein encoded by this gene has nine SCRs with the first two repeats having heparin binding properties, a region within repeats 5-7 having heparin binding and C reactive protein binding properties, and the C-terminal repeats being similar to a complement component 3 b (C3b) binding domain. This protein co-localizes with C3, binds C3b in a dose-dependent manner, and is recruited to tissues damaged by C-reactive protein. Allelic variations in this gene have been associated, but not causally linked, with two different forms of kidney disease: membranoproliferative glomerulonephritis type II (MPGNII) and hemolytic uraemic syndrome (HUS). [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-196977290-T-A is Benign according to our data. Variant chr1-196977290-T-A is described in ClinVar as [Benign]. Clinvar id is 1268818.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR5	XM_011510020.3	c.67+2176T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR5	ENST00000699466.1	c.-198+2176T>A		intron_variant
CFHR5	ENST00000699467.1	n.127+1702T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.195 AC: 27142 AN: 139390 Hom.: 4252 Cov.: 29

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.0457

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.00139

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.195 AC: 27154 AN: 139436 Hom.: 4256 Cov.: 29 AF XY: 0.194 AC XY: 13046 AN XY: 67184

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.00139

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0825

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.174

Alfa AF: 0.0254 Hom.: 21

Asia WGS AF: 0.0660 AC: 226 AN: 3424

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9427660; hg19: chr1-196946420;