rs651646

Variant names:

• chr11-72218482-T-A
• rs651646
• NM_000803.5:c.-24-79T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-72218482-T-A
• chr11-72218482-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000803.5(FOLR2):​c.-24-79T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,294,736 control chromosomes in the GnomAD database, including 142,819 homozygotes. 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: 𝑓 0.52 (21364 hom., cov: 31)
  • Exomes 𝑓: 0.46 (121455 hom.)
• Consequence: FOLR2 NM_000803.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 12 publications found

Genes affected

FOLR2 (HGNC:3793): (folate receptor beta) The protein encoded by this gene is a member of the folate receptor (FOLR) family, and these genes exist in a cluster on chromosome 11. Members of this gene family have a high affinity for folic acid and for several reduced folic acid derivatives, and they mediate delivery of 5-methyltetrahydrofolate to the interior of cells. This protein has a 68% and 79% sequence homology with the FOLR1 and FOLR3 proteins, respectively. Although this protein was originally thought to be specific to placenta, it can also exist in other tissues, and it may play a role in the transport of methotrexate in synovial macrophages in rheumatoid arthritis patients. Multiple transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000803.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR2	NM_000803.5	MANE Select	c.-24-79T>A		intron	N/A	NP_000794.3	P14207
	FOLR2	NM_001113534.2		c.-24-79T>A		intron	N/A	NP_001107006.1	P14207
	FOLR2	NM_001113535.2		c.-12-91T>A		intron	N/A	NP_001107007.1	P14207

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR2	ENST00000298223.11	TSL:1 MANE Select	c.-24-79T>A		intron	N/A	ENSP00000298223.6	P14207
	FOLR2	ENST00000868542.1		c.-103T>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000538601.1
	FOLR2	ENST00000868542.1		c.-103T>A		5_prime_UTR	Exon 1 of 4	ENSP00000538601.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78409 AN: 151772 Hom.: 21318 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.456 AC: 521210 AN: 1142846 Hom.: 121455 AF XY: 0.459 AC XY: 262939 AN XY: 573414

African (AFR) AF: 0.707 AC: 18823 AN: 26618

American (AMR) AF: 0.349 AC: 12084 AN: 34586

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 12262 AN: 22000

East Asian (EAS) AF: 0.418 AC: 14547 AN: 34794

South Asian (SAS) AF: 0.539 AC: 38229 AN: 70924

European-Finnish (FIN) AF: 0.501 AC: 23387 AN: 46668

Middle Eastern (MID) AF: 0.483 AC: 1871 AN: 3870

European-Non Finnish (NFE) AF: 0.441 AC: 376618 AN: 853968

Other (OTH) AF: 0.473 AC: 23389 AN: 49418

GnomAD4 genome AF: 0.517 AC: 78513 AN: 151890 Hom.: 21364 Cov.: 31 AF XY: 0.521 AC XY: 38670 AN XY: 74234

African (AFR) AF: 0.699 AC: 28997 AN: 41464

American (AMR) AF: 0.384 AC: 5869 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1994 AN: 3464

East Asian (EAS) AF: 0.471 AC: 2417 AN: 5134

South Asian (SAS) AF: 0.549 AC: 2643 AN: 4816

European-Finnish (FIN) AF: 0.503 AC: 5291 AN: 10524

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29767 AN: 67908

Other (OTH) AF: 0.497 AC: 1048 AN: 2110

Alfa AF: 0.347 Hom.: 916

Bravo AF: 0.511

Asia WGS AF: 0.559 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.078
DANN	Benign	0.82
PhyloP100		-1.8
PromoterAI		-0.0083	Neutral
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: rs651646; hg19: chr11-71929526;