chr1-196913214-A-G

Variant names:

• chr1-196913214-A-G
• rs7522952
• NM_001201550.3:c.1180+292A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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 VariationId 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.

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.1180+292A>G		intron	N/A	NP_001188479.1
	CFHR4	NM_001201551.2		c.1177+292A>G		intron	N/A	NP_001188480.1
	CFHR4	NM_006684.5		c.439+292A>G		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.1180+292A>G		intron	N/A	ENSP00000477162.2
	CFHR4	ENST00000251424.8	TSL:1	c.439+292A>G		intron	N/A	ENSP00000251424.4
	CFHR4	ENST00000367416.6	TSL:2	c.1177+292A>G		intron	N/A	ENSP00000356386.2

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

African (AFR) AF: 0.0433 AC: 1783 AN: 41174

American (AMR) AF: 0.0823 AC: 1251 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.137 AC: 659 AN: 4812

European-Finnish (FIN) AF: 0.0827 AC: 870 AN: 10514

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7609 AN: 67894

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.104 Hom.: 1221

Bravo AF: 0.0824

Asia WGS AF: 0.0560 AC: 194 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.41
PhyloP100		-1.2
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: rs7522952; hg19: chr1-196882344;