Genetic Variant BTD:c.-17+4603T>C (chr3-15606497-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

24 publications found

Variant links:

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

BTD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTD	NM_001370658.1 link	c.-17+4603T>C		intron_variant	Intron 1 of 3	ENST00000643237.3	NP_001357587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTD	ENST00000643237.3 link	c.-17+4603T>C		intron_variant	Intron 1 of 3		NM_001370658.1	ENSP00000495254.2		P43251-4

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95353

AN:

152020

Hom.:

31484

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.627

AC:

95460

AN:

152138

Hom.:

31536

Cov.:

AF XY:

0.628

AC XY:

46671

AN XY:

74374

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1699

3398

5097

6796

8495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.560

Hom.:

92659

Bravo

AF:

0.647

Asia WGS

AF:

0.590

AC:

2047

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.13

(source)

DANN

Benign

0.31

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over