chr3-15606497-T-C

Position:

• chr3-15606497-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370658.1(BTD):​c.-17+4603T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,144 control chromosomes in the GnomAD database, including 31,537 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 0.63 (31536 hom., cov: 33)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: BTD NM_001370658.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

BTD (HGNC:1122): (biotinidase) The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTD	NM_001370658.1	c.-17+4603T>C		intron_variant		ENST00000643237.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTD	ENST00000643237.3	c.-17+4603T>C		intron_variant			NM_001370658.1	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95353 AN: 152020 Hom.: 31484 Cov.: 33

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.624

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.627 AC: 95460 AN: 152138 Hom.: 31536 Cov.: 33 AF XY: 0.628 AC XY: 46671 AN XY: 74374

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.628

Alfa AF: 0.544 Hom.: 38685

Bravo AF: 0.647

Asia WGS AF: 0.590 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.13
DANN	Benign	0.31

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

LitVar

Other links and lift over

dbSNP: rs7651039; hg19: chr3-15648004;