21-46153636-A-G

Variant names:

• chr21-46153636-A-G
• rs2839127
• NM_206965.2:c.238+513T>C

Variant summary

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

The NM_206965.2(FTCD):​c.238+513T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,218 control chromosomes in the GnomAD database, including 44,616 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 0.75 (44616 hom., cov: 35)
• Consequence: FTCD NM_206965.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 13 publications found

Genes affected

FTCD (HGNC:3974): (formimidoyltransferase cyclodeaminase) The protein encoded by this gene is a bifunctional enzyme that channels 1-carbon units from formiminoglutamate, a metabolite of the histidine degradation pathway, to the folate pool. Mutations in this gene are associated with glutamate formiminotransferase deficiency. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Dec 2009]

FTCD Gene-Disease associations (from GenCC):

• formiminoglutamic aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet, Laboratory for Molecular Medicine

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTCD	NM_206965.2	c.238+513T>C		intron_variant	Intron 2 of 13	ENST00000397746.8	NP_996848.1
FTCD	NM_001320412.2	c.238+513T>C		intron_variant	Intron 2 of 14		NP_001307341.1
FTCD	NM_006657.3	c.238+513T>C		intron_variant	Intron 2 of 14		NP_006648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTCD	ENST00000397746.8	c.238+513T>C		intron_variant	Intron 2 of 13	1	NM_206965.2	ENSP00000380854.3

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113416 AN: 152100 Hom.: 44604 Cov.: 35

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.777

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.745 AC: 113457 AN: 152218 Hom.: 44616 Cov.: 35 AF XY: 0.754 AC XY: 56139 AN XY: 74428

African (AFR) AF: 0.475 AC: 19695 AN: 41484

American (AMR) AF: 0.852 AC: 13045 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2937 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5102 AN: 5172

South Asian (SAS) AF: 0.815 AC: 3933 AN: 4828

European-Finnish (FIN) AF: 0.909 AC: 9647 AN: 10618

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56463 AN: 68016

Other (OTH) AF: 0.775 AC: 1636 AN: 2112

Alfa AF: 0.813 Hom.: 84711

Bravo AF: 0.732

Asia WGS AF: 0.839 AC: 2918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.43
DANN	Benign	0.39
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2839127; hg19: chr21-47573550;