Genetic Variant NM_206965.2:c.457-14G>A (chr21-46151751-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_206965.2(FTCD):c.457-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,612,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

FTCD
NM_206965.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.02

Publications

0 publications found

Variant links:

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 links:

FTCD-AS1 (HGNC:40243): (FTCD antisense RNA 1)

FTCD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 21-46151751-C-T is Benign according to our data. Variant chr21-46151751-C-T is described in ClinVar as Benign. ClinVar VariationId is 1600618.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000807 (123/152364) while in subpopulation AFR AF = 0.00274 (114/41586). AF 95% confidence interval is 0.00233. There are 0 homozygotes in GnomAd4. There are 59 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FTCD	NM_206965.2	MANE Select	c.457-14G>A	intron	N/A	NP_996848.1	O95954-1
FTCD	NM_001320412.2		c.457-14G>A	intron	N/A	NP_001307341.1	O95954-2
FTCD	NM_006657.3		c.457-14G>A	intron	N/A	NP_006648.1	O95954-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FTCD	ENST00000397746.8	TSL:1 MANE Select	c.457-14G>A	intron	N/A	ENSP00000380854.3	O95954-1
FTCD	ENST00000397748.5	TSL:1	c.457-14G>A	intron	N/A	ENSP00000380856.1	O95954-2
FTCD	ENST00000291670.9	TSL:1	c.457-14G>A	intron	N/A	ENSP00000291670.5	O95954-1

Frequencies

GnomAD3 genomes

AF:

0.000808

AC:

123

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000302

AC:

AN:

247946

AF XY:

0.000297

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000603

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000809

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000223

AC:

325

AN:

1460062

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

148

AN XY:

726310

show subpopulations

African (AFR)

AF:

0.00341

AC:

114

AN:

33460

American (AMR)

AF:

0.000268

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26118

East Asian (EAS)

AF:

0.000176

AC:

AN:

39694

South Asian (SAS)

AF:

0.000197

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52090

Middle Eastern (MID)

AF:

0.000719

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

0.000107

AC:

119

AN:

1111862

Other (OTH)

AF:

0.000613

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000807

AC:

123

AN:

152364

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00274

AC:

114

AN:

41586

American (AMR)

AF:

0.000131

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000986

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glutamate formiminotransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.37

(source)

DANN

Benign

0.70

PhyloP100

-2.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over