1-196982740-A-G

Variant names:

• chr1-196982740-A-G
• rs76216631
• NM_030787.4:c.59-145A>G

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.59-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 721,134 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (90 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (36 hom.)
• Consequence: CFHR5 NM_030787.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58
• Publications: 0 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=-0.95).
• BP6: Variant 1-196982740-A-G is Benign according to our data. Variant chr1-196982740-A-G is described in ClinVar as [Benign]. Clinvar id is 1222004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR5	NM_030787.4	c.59-145A>G		intron_variant	Intron 1 of 9	ENST00000256785.5	NP_110414.1
CFHR5	XM_011510020.3	c.68-145A>G		intron_variant	Intron 1 of 9		XP_011508322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR5	ENST00000256785.5	c.59-145A>G		intron_variant	Intron 1 of 9	1	NM_030787.4	ENSP00000256785.4
CFHR5	ENST00000699466.1	c.-197-145A>G		intron_variant	Intron 1 of 9			ENSP00000514393.1
CFHR5	ENST00000699468.1	c.-25+5060A>G		intron_variant	Intron 1 of 5			ENSP00000514394.1
CFHR5	ENST00000699467.1	n.128-145A>G		intron_variant	Intron 1 of 9

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2844 AN: 152168 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00845

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00212 AC: 1207 AN: 568848 Hom.: 36 AF XY: 0.00169 AC XY: 514 AN XY: 304476

African (AFR) AF: 0.0640 AC: 933 AN: 14588

American (AMR) AF: 0.00409 AC: 107 AN: 26186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17500

East Asian (EAS) AF: 0.00 AC: 0 AN: 31876

South Asian (SAS) AF: 0.0000910 AC: 5 AN: 54970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40564

Middle Eastern (MID) AF: 0.00149 AC: 4 AN: 2678

European-Non Finnish (NFE) AF: 0.0000914 AC: 32 AN: 350272

Other (OTH) AF: 0.00417 AC: 126 AN: 30214

GnomAD4 genome AF: 0.0187 AC: 2841 AN: 152286 Hom.: 90 Cov.: 32 AF XY: 0.0171 AC XY: 1274 AN XY: 74452

African (AFR) AF: 0.0644 AC: 2674 AN: 41552

American (AMR) AF: 0.00843 AC: 129 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68026

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.0146 Hom.: 4

Bravo AF: 0.0217

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

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	-0.95
CADD	Benign	0.016
DANN	Benign	0.61
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs76216631; hg19: chr1-196951870; COSMIC: COSV56821944;