1-196910875-C-T

Variant names:

• chr1-196910875-C-T
• rs1409153
• NM_001201550.3:c.997+397C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201550.3(CFHR4):​c.997+397C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 151,048 control chromosomes in the GnomAD database, including 40,779 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 0.72 (40779 hom., cov: 31)
• Consequence: CFHR4 NM_001201550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 7 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]

LOC105371675 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR4	NM_001201550.3	c.997+397C>T		intron_variant	Intron 6 of 9	ENST00000608469.6	NP_001188479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR4	ENST00000608469.6	c.997+397C>T		intron_variant	Intron 6 of 9	1	NM_001201550.3	ENSP00000477162.2
CFHR4	ENST00000251424.8	c.257-1865C>T		intron_variant	Intron 2 of 5	1		ENSP00000251424.4
CFHR4	ENST00000367416.6	c.994+397C>T		intron_variant	Intron 6 of 9	2		ENSP00000356386.2
CFHR4	ENST00000699463.1	n.1065+397C>T		intron_variant	Intron 7 of 10

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108111 AN: 150934 Hom.: 40722 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.716 AC: 108222 AN: 151048 Hom.: 40779 Cov.: 31 AF XY: 0.718 AC XY: 52964 AN XY: 73756

African (AFR) AF: 0.911 AC: 37316 AN: 40962

American (AMR) AF: 0.775 AC: 11744 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2410 AN: 3464

East Asian (EAS) AF: 0.939 AC: 4833 AN: 5148

South Asian (SAS) AF: 0.738 AC: 3547 AN: 4806

European-Finnish (FIN) AF: 0.545 AC: 5676 AN: 10418

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.597 AC: 40488 AN: 67810

Other (OTH) AF: 0.725 AC: 1519 AN: 2094

Alfa AF: 0.662 Hom.: 4453

Bravo AF: 0.744

Asia WGS AF: 0.810 AC: 2813 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.2
DANN	Benign	0.14
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1409153; hg19: chr1-196880005;