chr1-196898103-T-C

Position:

• chr1-196898103-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201550.3(CFHR4):​c.59-4315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 150,930 control chromosomes in the GnomAD database, including 8,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (8046 hom., cov: 31)
• Consequence: CFHR4 NM_001201550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR4	NM_001201550.3	c.59-4315T>C		intron_variant		ENST00000608469.6	NP_001188479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR4	ENST00000608469.6	c.59-4315T>C		intron_variant		1	NM_001201550.3	ENSP00000477162.2
CFHR4	ENST00000251424.8	c.59-4315T>C		intron_variant		1		ENSP00000251424.4
CFHR4	ENST00000367416.6	c.59-4318T>C		intron_variant		2		ENSP00000356386.2
CFHR4	ENST00000699463.1	n.150+90T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42741 AN: 150816 Hom.: 8044 Cov.: 31

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.283 AC: 42741 AN: 150930 Hom.: 8046 Cov.: 31 AF XY: 0.281 AC XY: 20742 AN XY: 73730

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.271

Alfa AF: 0.407 Hom.: 11902

Bravo AF: 0.256

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.44

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: rs6685931; hg19: chr1-196867233;