rs572975646

Variant names:

• chr21-46151878-C-G
• rs572975646
• NM_206965.2:c.456+14G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-46151878-C-G
• chr21-46151878-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_206965.2(FTCD):​c.456+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FTCD NM_206965.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 0 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-AS1 (HGNC:40243): (FTCD antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206965.2. 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
	FTCD	NM_206965.2	MANE Select	c.456+14G>C		intron	N/A	NP_996848.1	O95954-1
	FTCD	NM_001320412.2		c.456+14G>C		intron	N/A	NP_001307341.1	O95954-2
	FTCD	NM_006657.3		c.456+14G>C		intron	N/A	NP_006648.1	O95954-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTCD	ENST00000397746.8	TSL:1 MANE Select	c.456+14G>C		intron	N/A	ENSP00000380854.3	O95954-1
	FTCD	ENST00000397748.5	TSL:1	c.456+14G>C		intron	N/A	ENSP00000380856.1	O95954-2
	FTCD	ENST00000291670.9	TSL:1	c.456+14G>C		intron	N/A	ENSP00000291670.5	O95954-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1403106 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 693088

African (AFR) AF: 0.00 AC: 0 AN: 31984

American (AMR) AF: 0.00 AC: 0 AN: 36648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 36460

South Asian (SAS) AF: 0.00 AC: 0 AN: 80680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081022

Other (OTH) AF: 0.00 AC: 0 AN: 57960

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.43
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs572975646; hg19: chr21-47571792;