3-15606497-T-C

Variant names:

• chr3-15606497-T-C
• rs7651039
• NM_001370658.1:c.-17+4603T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001407371.1(BTD):​c.-686T>C variant causes a 5 prime UTR 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_001407371.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 24 publications found

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]

BTD Gene-Disease associations (from GenCC):

• biotinidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001407371.1. 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
	BTD	NM_001370658.1	MANE Select	c.-17+4603T>C		intron	N/A	NP_001357587.1	P43251-4
	BTD	NM_001407371.1		c.-686T>C		5_prime_UTR	Exon 2 of 5	NP_001394300.1	P43251-4
	BTD	NM_001281723.4		c.-17+4727T>C		intron	N/A	NP_001268652.2	P43251-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTD	ENST00000643237.3	MANE Select	c.-17+4603T>C		intron	N/A	ENSP00000495254.2	P43251-4
	BTD	ENST00000303498.10	TSL:1	c.-293+4603T>C		intron	N/A	ENSP00000306477.6	P43251-4
	BTD	ENST00000427382.2	TSL:4	c.-17+4850T>C		intron	N/A	ENSP00000397113.2	P43251-4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.846 AC: 35106 AN: 41518

American (AMR) AF: 0.631 AC: 9650 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3468

East Asian (EAS) AF: 0.695 AC: 3609 AN: 5190

South Asian (SAS) AF: 0.540 AC: 2608 AN: 4832

European-Finnish (FIN) AF: 0.525 AC: 5542 AN: 10558

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35025 AN: 67980

Other (OTH) AF: 0.628 AC: 1324 AN: 2108

Alfa AF: 0.560 Hom.: 92659

Bravo AF: 0.647

Asia WGS AF: 0.590 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.13
DANN	Benign	0.31
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7651039; hg19: chr3-15648004;