11-72139110-CTA-C

Position:

• chr11-72139110-CTA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000804.4(FOLR3):​c.320_321del​(p.Tyr107Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,613,676 control chromosomes in the GnomAD database, including 681,325 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.87 (58449 hom., cov: 0)
  • Exomes 𝑓: 0.92 (622876 hom.)
• Consequence: FOLR3 NM_000804.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.80

Genes affected

FOLR3 (HGNC:3795): (folate receptor gamma) This gene encodes a member of the folate receptor (FOLR) family of proteins, which have a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells. Expression of this gene may be elevated in ovarian and primary peritoneal carcinoma. This gene is present in a gene cluster on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-72139110-CTA-C is Benign according to our data. Variant chr11-72139110-CTA-C is described in ClinVar as [Benign]. Clinvar id is 768461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR3	NM_000804.4	c.320_321del	p.Tyr107Ter	frameshift_variant	3/5	ENST00000611028.3	NP_000795.2
FOLR3	NR_178088.1	n.498_499del		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLR3	ENST00000611028.3	c.320_321del	p.Tyr107Ter	frameshift_variant	3/5	1	NM_000804.4	ENSP00000481114	P1
FOLR3	ENST00000612844.4	c.448_449del	p.Met150GlufsTer139	frameshift_variant, NMD_transcript_variant	3/5	1		ENSP00000481027
FOLR3	ENST00000622388.4	c.320_321del	p.Tyr107Ter	frameshift_variant	4/6	5		ENSP00000481833

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132711 AN: 151980 Hom.: 58426 Cov.: 0

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.902

GnomAD4 exome AF: 0.923 AC: 1348482 AN: 1461578 Hom.: 622876 AF XY: 0.924 AC XY: 671815 AN XY: 727058

Gnomad4 AFR exome AF: 0.746

Gnomad4 AMR exome AF: 0.945

Gnomad4 ASJ exome AF: 0.932

Gnomad4 EAS exome AF: 0.926

Gnomad4 SAS exome AF: 0.951

Gnomad4 FIN exome AF: 0.882

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.914

GnomAD4 genome AF: 0.873 AC: 132773 AN: 152098 Hom.: 58449 Cov.: 0 AF XY: 0.873 AC XY: 64910 AN XY: 74364

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.924

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.951

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.902

Alfa AF: 0.371 Hom.: 5677

Bravo AF: 0.873

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71891516; hg19: chr11-71850156;