Variant chr21-46136261-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000494498(FTCD):c.*236C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 591,536 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 30)

Exomes 𝑓: 0.00060 ( 2 hom. )

Consequence

FTCD
ENST00000494498 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.271

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 21-46136261-G-A is Benign according to our data. Variant chr21-46136261-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 369369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0049 (746/152238) while in subpopulation AFR AF= 0.017 (705/41542). AF 95% confidence interval is 0.0159. There are 4 homozygotes in gnomad4. There are 328 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
	use as main transcript	n.46136261G>A	intergenic_region
FTCD	NM_001320412.2 linkuse as main transcript	c.*193C>T	downstream_gene_variant	NP_001307341.1	O95954-2
FTCD	NM_006657.3 linkuse as main transcript	c.*236C>T	downstream_gene_variant	NP_006648.1	O95954-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
FTCD	ENST00000494498 linkuse as main transcript	c.*236C>T	3_prime_UTR_variant	6/6	3	ENSP00000507847.1	A0A804HKA5
FTCD	ENST00000397748.5 linkuse as main transcript	c.*193C>T	downstream_gene_variant		1	ENSP00000380856.1	O95954-2
FTCD	ENST00000291670.9 linkuse as main transcript	c.*236C>T	downstream_gene_variant		1	ENSP00000291670.5	O95954-1

Frequencies

GnomAD3 genomes

AF:

0.00490

AC:

746

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00431

GnomAD4 exome

AF:

0.000601

AC:

264

AN:

439298

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

117

AN XY:

229250

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.000751

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000455

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.00490

AC:

746

AN:

152238

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

328

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00341

Hom.:

Bravo

AF:

0.00559

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Myosclerosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Collagen 6-related myopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

DANN

Benign

0.57

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over