dbSNP rs3817641: BTD:p.Cys451Cys (chr3-15645269-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370658.1(BTD):c.1353T>C(p.Cys451Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,614,080 control chromosomes in the GnomAD database, including 9,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 967 hom., cov: 32)

Exomes 𝑓: 0.099 ( 8961 hom. )

Consequence

BTD
NM_001370658.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.203

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 3-15645269-T-C is Benign according to our data. Variant chr3-15645269-T-C is described in ClinVar as [Benign]. Clinvar id is 25088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-15645269-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.203 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTD	NM_001370658.1 link	c.1353T>C	p.Cys451Cys	synonymous_variant	Exon 4 of 4	ENST00000643237.3	NP_001357587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTD	ENST00000643237.3 link	c.1353T>C	p.Cys451Cys	synonymous_variant	Exon 4 of 4		NM_001370658.1	ENSP00000495254.2		P43251-4

Frequencies

GnomAD3 genomes

AF:

0.0959

AC:

14585

AN:

152080

Hom.:

958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0709

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.0822

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0860

Gnomad OTH

AF:

0.0965

GnomAD3 exomes

AF:

0.126

AC:

31678

AN:

251426

Hom.:

2842

AF XY:

0.124

AC XY:

16792

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0727

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.0474

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.0833

Gnomad NFE exome

AF:

0.0885

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0987

AC:

144351

AN:

1461882

Hom.:

8961

Cov.:

AF XY:

0.0995

AC XY:

72394

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0653

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.0475

Gnomad4 EAS exome

AF:

0.331

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.0876

Gnomad4 NFE exome

AF:

0.0867

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.0959

AC:

14600

AN:

152198

Hom.:

967

Cov.:

AF XY:

0.0981

AC XY:

7304

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0707

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.0822

Gnomad4 NFE

AF:

0.0860

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0872

Hom.:

864

Bravo

AF:

0.0987

Asia WGS

AF:

0.276

AC:

956

AN:

3478

EpiCase

AF:

0.0782

EpiControl

AF:

0.0860

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Biotinidase deficiency

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:3

Aug 31, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 20, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.3

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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