Variant chr1-196902587-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001201550.3(CFHR4):c.228T>C(p.Asp76=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,612,242 control chromosomes in the GnomAD database, including 322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 22 hom., cov: 32)

Exomes 𝑓: 0.012 ( 300 hom. )

Consequence

CFHR4
NM_001201550.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.36

Variant links:

Genes affected

CFHR4 (HGNC:16979): (complement factor H related 4) This gene is a member of the complement factor H (CFH) gene family, and encodes one of the 5 CFH-related (CFHR) proteins. These 5 genes are closely linked to the CFH gene on chromosome 1q31-q32. The CFHRs are secreted plasma proteins synthesized primarily by the hepatocytes, and composed of highly-related short consensus repeats (SCRs). This protein enhances the cofactor activity of CFH, and is involved in complement regulation. It can associate with lipoproteins and may play a role in lipid metabolism. Alternatively spliced transcript variants encoding different isoforms (varying in the number of SCRs) have been described for this gene. [provided by RefSeq, Jan 2011]

CFHR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-196902587-T-C is Benign according to our data. Variant chr1-196902587-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 788946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196902587-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.36 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 22 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR4	NM_001201550.3 linkuse as main transcript	c.228T>C	p.Asp76=	synonymous_variant	2/10	ENST00000608469.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR4	ENST00000608469.6 linkuse as main transcript	c.228T>C	p.Asp76=	synonymous_variant	2/10	1	NM_001201550.3	P4	Q92496-1

Frequencies

GnomAD3 genomes

AF:

0.00842

AC:

1275

AN:

151402

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00276

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00580

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00797

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00577

GnomAD3 exomes

AF:

0.00798

AC:

1996

AN:

250044

Hom.:

AF XY:

0.00799

AC XY:

1084

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.00316

Gnomad AMR exome

AF:

0.00506

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00451

Gnomad FIN exome

AF:

0.00565

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.00940

GnomAD4 exome

AF:

0.0119

AC:

17323

AN:

1460728

Hom.:

300

Cov.:

AF XY:

0.0114

AC XY:

8294

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.00213

Gnomad4 AMR exome

AF:

0.00539

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00479

Gnomad4 FIN exome

AF:

0.00512

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00841

AC:

1274

AN:

151514

Hom.:

Cov.:

AF XY:

0.00785

AC XY:

581

AN XY:

74038

show subpopulations

Gnomad4 AFR

AF:

0.00275

Gnomad4 AMR

AF:

0.00580

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00333

Gnomad4 FIN

AF:

0.00797

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00571

Alfa

AF:

0.00961

Hom.:

Bravo

AF:

0.00842

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0139

EpiControl

AF:

0.0122

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	CFHR4: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jul 08, 2021

- -

Atypical hemolytic-uremic syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 26, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.45

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over