1-196943816-C-G

Position:

• chr1-196943816-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005666.4(CFHR2):​c.-65C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (49 hom., cov: 4)
  • Exomes 𝑓: 0.065 (916 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR2 NM_005666.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.443

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]

CFHR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-196943816-C-G is Benign according to our data. Variant chr1-196943816-C-G is described in ClinVar as [Benign]. Clinvar id is 1288324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR2	NM_005666.4	c.-65C>G		5_prime_UTR_variant	1/5	ENST00000367415.8	NP_005657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR2	ENST00000367415	c.-65C>G		5_prime_UTR_variant	1/5	1	NM_005666.4	ENSP00000356385.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 913 AN: 17638 Hom.: 49 Cov.: 4 FAILED QC

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0349

Gnomad NFE AF: 0.0565

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0649 AC: 13112 AN: 201890 Hom.: 916 Cov.: 0 AF XY: 0.0658 AC XY: 7088 AN XY: 107784

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.0926

Gnomad4 ASJ exome AF: 0.0301

Gnomad4 EAS exome AF: 0.0630

Gnomad4 SAS exome AF: 0.0843

Gnomad4 FIN exome AF: 0.0485

Gnomad4 NFE exome AF: 0.0632

Gnomad4 OTH exome AF: 0.0568

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0519 AC: 915 AN: 17632 Hom.: 49 Cov.: 4 AF XY: 0.0537 AC XY: 410 AN XY: 7640

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0579

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0565

Gnomad4 OTH AF: 0.0323

Alfa AF: 0.00347 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.36

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: rs200227895; hg19: chr1-196912946;