chr1-196949662-C-T

Variant names:

• chr1-196949662-C-T
• rs112814481
• NM_005666.4:c.253+13C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_005666.4(CFHR2):​c.253+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,613,228 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0063 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00066 (15 hom.)
• Consequence: CFHR2 NM_005666.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.0640
• Publications: 1 publications found

Genes affected

CFHR2 (HGNC:4890): (complement factor H related 2) This gene belongs to a family of complement factor H-related genes (CFHR), which are clustered together with complement factor H gene on chromosome 1, and are involved in regulation of complement. Mutations in CFHR genes have been associated with dense deposit disease and atypical haemolytic-uraemic syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-196949662-C-T is Benign according to our data. Variant chr1-196949662-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1299802.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00633 (963/152214) while in subpopulation AFR AF = 0.0216 (895/41528). AF 95% confidence interval is 0.0204. There are 9 homozygotes in GnomAd4. There are 446 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005666.4. 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
	CFHR2	NM_005666.4	MANE Select	c.253+13C>T		intron	N/A	NP_005657.1	P36980-1
	CFHR2	NM_001410924.1		c.59-1190C>T		intron	N/A	NP_001397853.1	A0A3B3IRW0
	CFHR2	NM_001312672.1		c.58+5724C>T		intron	N/A	NP_001299601.1	A0A3B3IS28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	ENST00000367415.8	TSL:1 MANE Select	c.253+13C>T		intron	N/A	ENSP00000356385.4	P36980-1
	CFHR2	ENST00000367421.5	TSL:1	c.508+13C>T		intron	N/A	ENSP00000356391.4	A0A3B3IQ51
	CFHR2	ENST00000473386.1	TSL:1	c.58+5724C>T		intron	N/A	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes AF: 0.00632 AC: 962 AN: 152098 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00159 AC: 400 AN: 250874 AF XY: 0.00121

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000658 AC: 962 AN: 1461014 Hom.: 15 Cov.: 31 AF XY: 0.000608 AC XY: 442 AN XY: 726834

African (AFR) AF: 0.0216 AC: 724 AN: 33442

American (AMR) AF: 0.00146 AC: 65 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86234

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53412

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5758

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111370

Other (OTH) AF: 0.00182 AC: 110 AN: 60356

GnomAD4 genome AF: 0.00633 AC: 963 AN: 152214 Hom.: 9 Cov.: 33 AF XY: 0.00599 AC XY: 446 AN XY: 74408

African (AFR) AF: 0.0216 AC: 895 AN: 41528

American (AMR) AF: 0.00275 AC: 42 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68020

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00331 Hom.: 0

Bravo AF: 0.00706

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	14
DANN	Benign	0.64
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs112814481; hg19: chr1-196918792; COSMIC: COSV66382431;