chr1-196993876-T-A

Variant names:

• chr1-196993876-T-A
• rs10922152
• NM_030787.4:c.431-204T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030787.4(CFHR5):​c.431-204T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,126 control chromosomes in the GnomAD database, including 12,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (12816 hom., cov: 32)
• Consequence: CFHR5 NM_030787.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• Publications: 8 publications found

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]

CFHR5 Gene-Disease associations (from GenCC):

• C3 glomerulonephritis

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-196993876-T-A is Benign according to our data. Variant chr1-196993876-T-A is described in ClinVar as Benign. ClinVar VariationId is 1243356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR5	NM_030787.4	c.431-204T>A		intron_variant	Intron 3 of 9	ENST00000256785.5	NP_110414.1
CFHR5	XM_011510020.3	c.440-204T>A		intron_variant	Intron 3 of 9		XP_011508322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR5	ENST00000256785.5	c.431-204T>A		intron_variant	Intron 3 of 9	1	NM_030787.4	ENSP00000256785.4
CFHR5	ENST00000699466.1	c.176-204T>A		intron_variant	Intron 3 of 9			ENSP00000514393.1
CFHR5	ENST00000699468.1	c.-24-2238T>A		intron_variant	Intron 1 of 5			ENSP00000514394.1
CFHR5	ENST00000699467.1	n.500-204T>A		intron_variant	Intron 3 of 9

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58247 AN: 152006 Hom.: 12805 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.383 AC: 58267 AN: 152126 Hom.: 12816 Cov.: 32 AF XY: 0.377 AC XY: 28021 AN XY: 74362

African (AFR) AF: 0.191 AC: 7945 AN: 41512

American (AMR) AF: 0.342 AC: 5230 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3468

East Asian (EAS) AF: 0.130 AC: 670 AN: 5172

South Asian (SAS) AF: 0.378 AC: 1818 AN: 4814

European-Finnish (FIN) AF: 0.456 AC: 4820 AN: 10576

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34742 AN: 67990

Other (OTH) AF: 0.389 AC: 822 AN: 2114

Alfa AF: 0.442 Hom.: 1962

Bravo AF: 0.366

Asia WGS AF: 0.248 AC: 861 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.51
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10922152; hg19: chr1-196963006; COSMIC: COSV56819754;