rs6685931

Variant names:

• chr1-196898103-T-C
• rs6685931
• NM_001201550.3:c.59-4315T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201550.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR4	NM_001201550.3	MANE Select	c.59-4315T>C		intron	N/A	NP_001188479.1
	CFHR4	NM_001201551.2		c.59-4318T>C		intron	N/A	NP_001188480.1
	CFHR4	NM_006684.5		c.59-4315T>C		intron	N/A	NP_006675.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR4	ENST00000608469.6	TSL:1 MANE Select	c.59-4315T>C		intron	N/A	ENSP00000477162.2
	CFHR4	ENST00000251424.8	TSL:1	c.59-4315T>C		intron	N/A	ENSP00000251424.4
	CFHR4	ENST00000367416.6	TSL:2	c.59-4318T>C		intron	N/A	ENSP00000356386.2

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

African (AFR) AF: 0.0891 AC: 3643 AN: 40878

American (AMR) AF: 0.225 AC: 3403 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1055 AN: 3464

East Asian (EAS) AF: 0.0607 AC: 313 AN: 5156

South Asian (SAS) AF: 0.262 AC: 1255 AN: 4796

European-Finnish (FIN) AF: 0.455 AC: 4721 AN: 10380

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27268 AN: 67792

Other (OTH) AF: 0.271 AC: 570 AN: 2106

Alfa AF: 0.404 Hom.: 12547

Bravo AF: 0.256

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.44
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6685931; hg19: chr1-196867233;