1-196917640-T-C

Position:

• chr1-196917640-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.1541-570T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 150,876 control chromosomes in the GnomAD database, including 5,876 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 0.23 (5876 hom., cov: 31)
• Consequence: CFHR4 NM_001201550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR4	NM_001201550.3	c.1541-570T>C		intron_variant		ENST00000608469.6
LOC105371675	XR_007066779.1	n.375-4957A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR4	ENST00000608469.6	c.1541-570T>C		intron_variant		1	NM_001201550.3	P4
CFHR4	ENST00000251424.8	c.800-570T>C		intron_variant		1
CFHR4	ENST00000367416.6	c.1538-570T>C		intron_variant		2		A2
CFHR4	ENST00000699463.1	n.1609-570T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35061 AN: 150762 Hom.: 5870 Cov.: 31

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.232 AC: 35069 AN: 150876 Hom.: 5876 Cov.: 31 AF XY: 0.243 AC XY: 17934 AN XY: 73752

Gnomad4 AFR AF: 0.0673

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.250

Alfa AF: 0.180 Hom.: 625

Bravo AF: 0.236

Asia WGS AF: 0.505 AC: 1751 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.36

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: rs4915559; hg19: chr1-196886770;