Variant 1-196902602-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001201550.3(CFHR4):c.243G>A(p.Thr81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,610,032 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0091 ( 64 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 55 hom. )

Consequence

CFHR4
NM_001201550.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.907

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-196902602-G-A is Benign according to our data. Variant chr1-196902602-G-A is described in ClinVar as [Benign]. Clinvar id is 1336563.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-196902602-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.907 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00913 (1382/151328) while in subpopulation AFR AF= 0.0322 (1322/41008). AF 95% confidence interval is 0.0308. There are 64 homozygotes in gnomad4. There are 650 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR4	NM_001201550.3 linkuse as main transcript	c.243G>A	p.Thr81=	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.243G>A	p.Thr81=	synonymous_variant	2/10	1	NM_001201550.3	P4	Q92496-1

Frequencies

GnomAD3 genomes

AF:

0.00909

AC:

1375

AN:

151218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00277

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00577

GnomAD3 exomes

AF:

0.00215

AC:

538

AN:

249666

Hom.:

AF XY:

0.00158

AC XY:

214

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.000991

GnomAD4 exome

AF:

0.000899

AC:

1312

AN:

1458704

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

552

AN XY:

725906

show subpopulations

Gnomad4 AFR exome

AF:

0.0318

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00913

AC:

1382

AN:

151328

Hom.:

Cov.:

AF XY:

0.00879

AC XY:

650

AN XY:

73934

show subpopulations

Gnomad4 AFR

AF:

0.0322

Gnomad4 AMR

AF:

0.00277

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00571

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.0100

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000548

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 14, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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