1-196977900-T-C

Variant names:

• chr1-196977900-T-C
• rs12755054
• NM_030787.4:c.58+178T>C

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.58+178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,040 control chromosomes in the GnomAD database, including 15,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (15588 hom., cov: 32)
• Consequence: CFHR5 NM_030787.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82
• Publications: 4 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=-0.97).
• BP6: Variant 1-196977900-T-C is Benign according to our data. Variant chr1-196977900-T-C is described in ClinVar as [Benign]. Clinvar id is 1248903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR5	NM_030787.4	c.58+178T>C		intron_variant	Intron 1 of 9	ENST00000256785.5	NP_110414.1
CFHR5	XM_011510020.3	c.67+2786T>C		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.58+178T>C		intron_variant	Intron 1 of 9	1	NM_030787.4	ENSP00000256785.4
CFHR5	ENST00000699466.1	c.-198+2786T>C		intron_variant	Intron 1 of 9			ENSP00000514393.1
CFHR5	ENST00000699468.1	c.-25+220T>C		intron_variant	Intron 1 of 5			ENSP00000514394.1
CFHR5	ENST00000699467.1	n.127+2312T>C		intron_variant	Intron 1 of 9

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63568 AN: 151924 Hom.: 15565 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.418 AC: 63628 AN: 152040 Hom.: 15588 Cov.: 32 AF XY: 0.413 AC XY: 30675 AN XY: 74326

African (AFR) AF: 0.691 AC: 28625 AN: 41454

American (AMR) AF: 0.312 AC: 4771 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1367 AN: 3472

East Asian (EAS) AF: 0.180 AC: 932 AN: 5182

South Asian (SAS) AF: 0.303 AC: 1456 AN: 4806

European-Finnish (FIN) AF: 0.293 AC: 3097 AN: 10570

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22224 AN: 67964

Other (OTH) AF: 0.406 AC: 858 AN: 2112

Alfa AF: 0.305 Hom.: 4549

Bravo AF: 0.430

Asia WGS AF: 0.252 AC: 876 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 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	-0.97
CADD	Benign	0.11
DANN	Benign	0.24
PhyloP100		-1.8
PromoterAI		0.0070	Neutral
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: rs12755054; hg19: chr1-196947030;