21-46136261-G-A

Position:

• chr21-46136261-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.271

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]

(HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.46136261G>A		intergenic_region
FTCD	NM_001320412.2	c.*193C>T		downstream_gene_variant			NP_001307341.1
FTCD	NM_006657.3	c.*236C>T		downstream_gene_variant			NP_006648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTCD	ENST00000494498	c.*236C>T		3_prime_UTR_variant	6/6	3		ENSP00000507847.1
FTCD	ENST00000397748.5	c.*193C>T		downstream_gene_variant		1		ENSP00000380856.1
FTCD	ENST00000291670.9	c.*236C>T		downstream_gene_variant		1		ENSP00000291670.5

Frequencies

GnomAD3 genomes AF: 0.00490 AC: 746 AN: 152120 Hom.: 4 Cov.: 30

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.: 2 Cov.: 4 AF XY: 0.000510 AC XY: 117 AN XY: 229250

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.: 4 Cov.: 30 AF XY: 0.00441 AC XY: 328 AN XY: 74442

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.: 0

Bravo AF: 0.00559

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

Other links and lift over

dbSNP: rs77991819; hg19: chr21-47556175;