1-196944067-C-G

Position:

• chr1-196944067-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.58+129C>G variant causes a intron 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 0.37 (9176 hom., cov: 15)
  • Exomes 𝑓: 0.41 (27019 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR2 NM_005666.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.258

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=-0.9).
• BP6: Variant 1-196944067-C-G is Benign according to our data. Variant chr1-196944067-C-G is described in ClinVar as [Benign]. Clinvar id is 1271113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFHR2	NM_005666.4	c.58+129C>G		intron_variant		ENST00000367415.8	NP_005657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR2	ENST00000367415.8	c.58+129C>G		intron_variant		1	NM_005666.4	ENSP00000356385.4

Frequencies

GnomAD3 genomes AF: 0.368 AC: 35058 AN: 95394 Hom.: 9169 Cov.: 15

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.394

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.413 AC: 90825 AN: 219686 Hom.: 27019 AF XY: 0.415 AC XY: 48494 AN XY: 116774

Gnomad4 AFR exome AF: 0.526

Gnomad4 AMR exome AF: 0.600

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.827

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.368 AC: 35076 AN: 95428 Hom.: 9176 Cov.: 15 AF XY: 0.381 AC XY: 17605 AN XY: 46244

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.390

Alfa AF: 0.325 Hom.: 1233

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 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.80

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: rs140103005; hg19: chr1-196913197; COSMIC: COSV66380837;