Variant 1-196902487-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001201550.3(CFHR4):c.128A>T(p.Tyr43Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000869 in 1,611,966 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 36 hom. )

Consequence

CFHR4
NM_001201550.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.740

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009356916).

BP6

Variant 1-196902487-A-T is Benign according to our data. Variant chr1-196902487-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1712456.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000607 (92/151600) while in subpopulation SAS AF= 0.0189 (91/4814). AF 95% confidence interval is 0.0158. There are 1 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 36 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR4	NM_001201550.3 linkuse as main transcript	c.128A>T	p.Tyr43Phe	missense_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.128A>T	p.Tyr43Phe	missense_variant	2/10	1	NM_001201550.3	P4	Q92496-1

Frequencies

GnomAD3 genomes

AF:

0.000607

AC:

AN:

151488

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00195

AC:

488

AN:

249776

Hom.:

AF XY:

0.00259

AC XY:

351

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000896

AC:

1308

AN:

1460366

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

921

AN XY:

726542

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.000607

AC:

AN:

151600

Hom.:

Cov.:

AF XY:

0.000931

AC XY:

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0189

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.00216

AC:

261

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Atypical hemolytic-uremic syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.8

DANN

Benign

0.95

DEOGEN2

Benign

0.035

.;T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.60

T;T;T;T

MetaRNN

Benign

0.0094

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.0

.;M;M;.

MutationTaster

Benign

1.0

D;D;N;N

PROVEAN

Benign

-0.98

N;.;N;N

REVEL

Benign

0.11

Sift

Benign

0.87

T;.;T;T

Sift4G

Benign

0.52

T;.;T;T

Polyphen

1.0

.;D;.;.

Vest4

0.19

MutPred

0.59

.;Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);

MVP

0.39

MPC

0.39

ClinPred

0.027

GERP RS

3.4

Varity_R

0.090

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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