1-196951169-T-C

Variant names:

• chr1-196951169-T-C
• rs3790414
• NM_005666.4:c.430+141T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005666.4(CFHR2):​c.430+141T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR2 NM_005666.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	NM_005666.4	MANE Select	c.430+141T>C		intron	N/A	NP_005657.1
	CFHR2	NM_001410924.1		c.235+141T>C		intron	N/A	NP_001397853.1
	CFHR2	NM_001312672.1		c.59-6722T>C		intron	N/A	NP_001299601.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	ENST00000367415.8	TSL:1 MANE Select	c.430+141T>C		intron	N/A	ENSP00000356385.4
	CFHR2	ENST00000367421.5	TSL:1	c.685+141T>C		intron	N/A	ENSP00000356391.4
	CFHR2	ENST00000473386.1	TSL:1	c.59-6722T>C		intron	N/A	ENSP00000497089.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 909786 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 457416

African (AFR) AF: 0.00 AC: 0 AN: 21278

American (AMR) AF: 0.00 AC: 0 AN: 22428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17232

East Asian (EAS) AF: 0.00 AC: 0 AN: 32846

South Asian (SAS) AF: 0.00 AC: 0 AN: 53786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3414

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 678514

Other (OTH) AF: 0.00 AC: 0 AN: 40920

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.90

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: rs3790414; hg19: chr1-196920299;