1-196888201-T-A

Position:

• chr1-196888201-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001201550.3(CFHR4):​c.51T>A​(p.Asn17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFHR4 NM_001201550.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.595

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076502055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR4	NM_001201550.3	c.51T>A	p.Asn17Lys	missense_variant	1/10	ENST00000608469.6	NP_001188479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR4	ENST00000608469.6	c.51T>A	p.Asn17Lys	missense_variant	1/10	1	NM_001201550.3	ENSP00000477162.2
CFHR4	ENST00000251424.8	c.51T>A	p.Asn17Lys	missense_variant	1/6	1		ENSP00000251424.4
CFHR4	ENST00000367416.6	c.51T>A	p.Asn17Lys	missense_variant	1/10	2		ENSP00000356386.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Sep 19, 2024

BP4, PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.070
DANN	Benign	0.71
DEOGEN2	Benign	0.023	.;T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.44	T;T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.077	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;N;.
PROVEAN	Benign	-0.11	N;.;N;N
REVEL	Benign	0.070
Sift	Benign	0.047	D;.;T;T
Sift4G	Benign	1.0	T;.;T;T
Polyphen		0.91	.;P;.;.
Vest4		0.077
MutPred		0.52		Gain of methylation at N17 (P = 0.0056);Gain of methylation at N17 (P = 0.0056);Gain of methylation at N17 (P = 0.0056);Gain of methylation at N17 (P = 0.0056);
MVP		0.15
MPC		0.088
ClinPred		0.18	T
GERP RS		-5.8
Varity_R		0.052
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-196857331;