1-196913214-A-G

Position:

• chr1-196913214-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001201550.3(CFHR4):​c.1180+292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 151,554 control chromosomes in the GnomAD database, including 788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.085 (788 hom., cov: 32)
• Consequence: CFHR4 NM_001201550.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-196913214-A-G is Benign according to our data. Variant chr1-196913214-A-G is described in ClinVar as [Benign]. Clinvar id is 1258081.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR4	NM_001201550.3	c.1180+292A>G		intron_variant		ENST00000608469.6	NP_001188479.1
LOC105371675	XR_007066779.1	n.375-531T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR4	ENST00000608469.6	c.1180+292A>G		intron_variant		1	NM_001201550.3	ENSP00000477162	P4
CFHR4	ENST00000251424.8	c.439+292A>G		intron_variant		1		ENSP00000251424
CFHR4	ENST00000367416.6	c.1177+292A>G		intron_variant		2		ENSP00000356386	A2
CFHR4	ENST00000699463.1	n.1248+292A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12877 AN: 151442 Hom.: 790 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0849 AC: 12868 AN: 151554 Hom.: 788 Cov.: 32 AF XY: 0.0850 AC XY: 6297 AN XY: 74070

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.0823

Gnomad4 ASJ AF: 0.0945

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0827

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.115

Alfa AF: 0.108 Hom.: 1019

Bravo AF: 0.0824

Asia WGS AF: 0.0560 AC: 194 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.41

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: rs7522952; hg19: chr1-196882344;