chr1-196912470-G-C

Variant names:

• chr1-196912470-G-C
• rs1853883
• NM_001201550.3:c.998-270G>C

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.998-270G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 150,768 control chromosomes in the GnomAD database, including 33,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (33447 hom., cov: 31)
• Consequence: CFHR4 NM_001201550.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214
• Publications: 14 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=-1.03).
• BP6: Variant 1-196912470-G-C is Benign according to our data. Variant chr1-196912470-G-C is described in ClinVar as Benign. ClinVar VariationId is 1237579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR4	NM_001201550.3	MANE Select	c.998-270G>C		intron	N/A	NP_001188479.1	Q92496-1
	CFHR4	NM_001201551.2		c.995-270G>C		intron	N/A	NP_001188480.1	Q92496-2
	CFHR4	NM_006684.5		c.257-270G>C		intron	N/A	NP_006675.2	Q92496-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR4	ENST00000608469.6	TSL:1 MANE Select	c.998-270G>C		intron	N/A	ENSP00000477162.2	Q92496-1
	CFHR4	ENST00000251424.8	TSL:1	c.257-270G>C		intron	N/A	ENSP00000251424.4	Q92496-3
	CFHR4	ENST00000367416.6	TSL:2	c.995-270G>C		intron	N/A	ENSP00000356386.2	Q92496-2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 97486 AN: 150650 Hom.: 33402 Cov.: 31

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.647 AC: 97580 AN: 150768 Hom.: 33447 Cov.: 31 AF XY: 0.651 AC XY: 47884 AN XY: 73578

African (AFR) AF: 0.810 AC: 33019 AN: 40768

American (AMR) AF: 0.709 AC: 10720 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2329 AN: 3468

East Asian (EAS) AF: 0.895 AC: 4594 AN: 5132

South Asian (SAS) AF: 0.654 AC: 3148 AN: 4810

European-Finnish (FIN) AF: 0.501 AC: 5202 AN: 10392

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36692 AN: 67764

Other (OTH) AF: 0.669 AC: 1403 AN: 2098

Alfa AF: 0.416 Hom.: 1012

Bravo AF: 0.672

Asia WGS AF: 0.760 AC: 2640 AN: 3478

ClinVar

ClinVar submissions

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	-1.0
CADD	Benign	0.65
DANN	Benign	0.14
PhyloP100		-0.21
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: rs1853883; hg19: chr1-196881600;