rs114567021

Variant names:

• chr3-15601817-C-T
• rs114567021
• NM_001370658.1:c.-94C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001281724.3(BTD):​c.-282C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,614,156 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (66 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (58 hom.)
• Consequence: BTD NM_001281724.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.808
• Publications: 1 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]

HACL1 (HGNC:17856): (2-hydroxyacyl-CoA lyase 1) Enables several functions, including 2-hydroxy-3-methylhexadecanoyl-CoA lyase activity; ATP binding activity; and cation binding activity. Involved in fatty acid alpha-oxidation; phytanic acid metabolic process; and protein targeting to peroxisome. Located in nucleoplasm and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-15601817-C-T is Benign according to our data. Variant chr3-15601817-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 25104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281724.3. 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.-94C>T		5_prime_UTR	Exon 1 of 4	NP_001357587.1
	BTD	NM_001281724.3		c.-282C>T		5_prime_UTR	Exon 1 of 6	NP_001268653.2
	BTD	NM_001323582.2		c.-370C>T		5_prime_UTR	Exon 1 of 5	NP_001310511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTD	ENST00000643237.3	MANE Select	c.-94C>T		5_prime_UTR	Exon 1 of 4	ENSP00000495254.2
	BTD	ENST00000303498.10	TSL:1	c.-370C>T		5_prime_UTR	Exon 1 of 5	ENSP00000306477.6
	HACL1	ENST00000900332.1		c.-354G>A		5_prime_UTR	Exon 1 of 16	ENSP00000570391.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2449 AN: 152202 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00462 AC: 1160 AN: 250904 AF XY: 0.00348

Gnomad AFR exome AF: 0.0549

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000547

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00204 AC: 2986 AN: 1461836 Hom.: 58 Cov.: 34 AF XY: 0.00178 AC XY: 1293 AN XY: 727208

African (AFR) AF: 0.0540 AC: 1807 AN: 33478

American (AMR) AF: 0.00635 AC: 284 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.000512 AC: 569 AN: 1112006

Other (OTH) AF: 0.00467 AC: 282 AN: 60394

GnomAD4 genome AF: 0.0161 AC: 2451 AN: 152320 Hom.: 66 Cov.: 33 AF XY: 0.0154 AC XY: 1145 AN XY: 74488

African (AFR) AF: 0.0528 AC: 2196 AN: 41564

American (AMR) AF: 0.0117 AC: 179 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68032

Other (OTH) AF: 0.0165 AC: 35 AN: 2116

Alfa AF: 0.00675 Hom.: 10

Bravo AF: 0.0193

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Biotinidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.2
DANN	Benign	0.71
PhyloP100		0.81
PromoterAI		0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs114567021; hg19: chr3-15643324;