1-196978009-C-T

Position:

• chr1-196978009-C-T

Variant summary

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

The NM_030787.4(CFHR5):​c.58+287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,970 control chromosomes in the GnomAD database, including 5,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (5263 hom., cov: 32)
• Consequence: CFHR5 NM_030787.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.135

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=-0.95).
• BP6: Variant 1-196978009-C-T is Benign according to our data. Variant chr1-196978009-C-T is described in ClinVar as [Benign]. Clinvar id is 1277859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR5	NM_030787.4	c.58+287C>T		intron_variant		ENST00000256785.5
CFHR5	XM_011510020.3	c.67+2895C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR5	ENST00000256785.5	c.58+287C>T		intron_variant		1	NM_030787.4	P1
CFHR5	ENST00000699466.1	c.-198+2895C>T		intron_variant
CFHR5	ENST00000699468.1	c.-25+329C>T		intron_variant
CFHR5	ENST00000699467.1	n.127+2421C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29715 AN: 151852 Hom.: 5246 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0902

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.196 AC: 29761 AN: 151970 Hom.: 5263 Cov.: 32 AF XY: 0.193 AC XY: 14302 AN XY: 74280

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.0902

Gnomad4 OTH AF: 0.172

Alfa AF: 0.0444 Hom.: 56

Bravo AF: 0.211

Asia WGS AF: 0.0730 AC: 255 AN: 3476

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

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.52

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: rs12731209; hg19: chr1-196947139;