1-196910875-C-T

Position:

• chr1-196910875-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
CFHR4	NM_001201550.3	c.997+397C>T		intron_variant		ENST00000608469.6
LOC105371675	XR_007066779.1	n.2183G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR4	ENST00000608469.6	c.997+397C>T		intron_variant		1	NM_001201550.3	P4
CFHR4	ENST00000251424.8	c.257-1865C>T		intron_variant		1
CFHR4	ENST00000367416.6	c.994+397C>T		intron_variant		2		A2
CFHR4	ENST00000699463.1	n.1065+397C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.725

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1409153; hg19: chr1-196880005;