rs114092911

Positions:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBS1BS2_Supporting

The NM_001370658.1(BTD):c.142A>G(p.Ile48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,614,192 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00062 ( 8 hom. )

Consequence

BTD
NM_001370658.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.728

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 links:

BTD (HGNC:):

BTD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063790977).

BP6

Variant 3-15635581-A-G is Benign according to our data. Variant chr3-15635581-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 528480.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 = 0.00659 (1004/152298) while in subpopulation AFR AF= 0.0229 (953/41568). AF 95% confidence interval is 0.0217. There are 9 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTD	NM_001370658.1 linkuse as main transcript	c.142A>G	p.Ile48Val	missense_variant	2/4	ENST00000643237.3	NP_001357587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTD	ENST00000643237.3 linkuse as main transcript	c.142A>G	p.Ile48Val	missense_variant	2/4		NM_001370658.1	ENSP00000495254.2		P43251-4

Frequencies

GnomAD3 genomes

AF:

0.00658

AC:

1002

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00147

AC:

370

AN:

251438

Hom.:

AF XY:

0.00111

AC XY:

151

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000621

AC:

908

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

365

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0225

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00659

AC:

1004

AN:

152298

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

475

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.00229

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:

0.00332

Alfa

AF:

0.000734

Hom.:

Bravo

AF:

0.00737

ESP6500AA

AF:

0.0225

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00191

AC:

232

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Biotinidase deficiency

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Aug 17, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

BTD-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 09, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

0.13

DANN

Benign

0.37

DEOGEN2

Benign

0.34

.;.;T;.;.;.;.;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

.;T;T;.;T;.;T;T;T;T

MetaRNN

Benign

0.0064

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.3

.;.;L;.;.;.;.;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.90

N;N;.;.;.;.;N;N;N;.

REVEL

Benign

0.17

Sift

Benign

0.54

T;T;.;.;.;.;T;T;T;.

Sift4G

Benign

0.36

T;T;.;.;.;.;T;T;T;.

Polyphen

0.0080

.;.;B;.;.;.;.;.;.;.

Vest4

0.093, 0.10

MVP

0.78

MPC

0.062

ClinPred

0.0011

GERP RS

-3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.016

gMVP

0.56

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

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