rs3790414

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-196951169-T-A
• chr1-196951169-T-C
• chr1-196951169-T-G

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 VariationId 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.

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>A		intron	N/A	NP_005657.1
	CFHR2	NM_001410924.1		c.235+141T>A		intron	N/A	NP_001397853.1
	CFHR2	NM_001312672.1		c.59-6722T>A		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>A		intron	N/A	ENSP00000356385.4
	CFHR2	ENST00000367421.5	TSL:1	c.685+141T>A		intron	N/A	ENSP00000356391.4
	CFHR2	ENST00000473386.1	TSL:1	c.59-6722T>A		intron	N/A	ENSP00000497089.1

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

African (AFR) AF: 0.183 AC: 3893 AN: 21254

American (AMR) AF: 0.461 AC: 10322 AN: 22386

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 4932 AN: 17224

East Asian (EAS) AF: 0.697 AC: 22876 AN: 32812

South Asian (SAS) AF: 0.287 AC: 15430 AN: 53708

European-Finnish (FIN) AF: 0.287 AC: 11254 AN: 39244

Middle Eastern (MID) AF: 0.185 AC: 631 AN: 3404

European-Non Finnish (NFE) AF: 0.210 AC: 142167 AN: 676824

Other (OTH) AF: 0.263 AC: 10751 AN: 40860

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

African (AFR) AF: 0.186 AC: 7735 AN: 41514

American (AMR) AF: 0.406 AC: 6195 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3472

East Asian (EAS) AF: 0.715 AC: 3697 AN: 5172

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4822

European-Finnish (FIN) AF: 0.304 AC: 3217 AN: 10572

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15886 AN: 67972

Other (OTH) AF: 0.273 AC: 578 AN: 2114

Alfa AF: 0.241 Hom.: 564

Bravo AF: 0.272

Asia WGS AF: 0.512 AC: 1776 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.86
DANN	Benign	0.29
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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;