1-196951169-T-A

Position:

• chr1-196951169-T-A

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.430+141T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,059,830 control chromosomes in the GnomAD database, including 39,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6293 hom., cov: 32)
  • Exomes 𝑓: 0.24 (33082 hom.)
• Consequence: CFHR2 NM_005666.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.898

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-196951169-T-A is Benign according to our data. Variant chr1-196951169-T-A is described in ClinVar as [Benign]. Clinvar id is 1288915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR2	NM_005666.4	c.430+141T>A		intron_variant		ENST00000367415.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR2	ENST00000367415.8	c.430+141T>A		intron_variant		1	NM_005666.4	P2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40140 AN: 151996 Hom.: 6289 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.245 AC: 222256 AN: 907716 Hom.: 33082 AF XY: 0.247 AC XY: 112637 AN XY: 456346

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.461

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.697

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.264 AC: 40154 AN: 152114 Hom.: 6293 Cov.: 32 AF XY: 0.274 AC XY: 20408 AN XY: 74374

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.273

Alfa AF: 0.241 Hom.: 564

Bravo AF: 0.272

Asia WGS AF: 0.512 AC: 1776 AN: 3472

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	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.86
DANN	Benign	0.29

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: rs3790414; hg19: chr1-196920299;