rs1853882

Positions:

• chr1-196916214-C-G

Variant summary

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

The NM_001201550.3(CFHR4):​c.1540+1076C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,170 control chromosomes in the GnomAD database, including 4,959 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 0.20 (4959 hom., cov: 32)
• Consequence: CFHR4 NM_001201550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609

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]

LOC105371675 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR4	NM_001201550.3	c.1540+1076C>G		intron_variant		ENST00000608469.6	NP_001188479.1
LOC105371675	XR_007066779.1	n.375-3531G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR4	ENST00000608469.6	c.1540+1076C>G		intron_variant		1	NM_001201550.3	ENSP00000477162	P4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 30947 AN: 151054 Hom.: 4953 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.205 AC: 30966 AN: 151170 Hom.: 4959 Cov.: 32 AF XY: 0.202 AC XY: 14882 AN XY: 73856

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.000777

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.205

Alfa AF: 0.170 Hom.: 451

Bravo AF: 0.215

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.37

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: rs1853882; hg19: chr1-196885344;