rs723587

Variant names:

• chr6-80346643-G-A
• rs723587
• NM_001424035.1:c.1039-7610G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-80346643-G-A
• chr6-80346643-G-C

Variant summary

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

The NM_001424035.1(BCKDHB):​c.1039-7610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,068 control chromosomes in the GnomAD database, including 1,881 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 0.14 (1881 hom., cov: 32)
• Consequence: BCKDHB NM_001424035.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 6 publications found

Genes affected

BCKDHB (HGNC:987): (branched chain keto acid dehydrogenase E1 subunit beta) This gene encodes the E1 beta subunit of branched-chain keto acid dehydrogenase, which is a multienzyme complex associated with the inner membrane of mitochondria. This enzyme complex functions in the catabolism of branched-chain amino acids. Mutations in this gene have been associated with maple syrup urine disease (MSUD), type 1B, a disease characterized by a maple syrup odor to the urine in addition to mental and physical retardation and feeding problems. Alternative splicing at this locus results in multiple transcript variants. [provided by RefSeq, Jan 2016]

BCKDHB Gene-Disease associations (from GenCC):

• maple syrup urine disease type 1B

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, G2P, Myriad Women’s Health
• maple syrup urine disease

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• classic maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intermediate maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intermittent maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• thiamine-responsive maple syrup urine disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCKDHB	NM_001424035.1	c.1039-7610G>A		intron_variant	Intron 9 of 9		NP_001410964.1
BCKDHB	NM_001424036.1	c.*8+2831G>A		intron_variant	Intron 10 of 10		NP_001410965.1
BCKDHB	NM_001424037.1	c.1038+73422G>A		intron_variant	Intron 9 of 9		NP_001410966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21869 AN: 151950 Hom.: 1885 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.144 AC: 21885 AN: 152068 Hom.: 1881 Cov.: 32 AF XY: 0.145 AC XY: 10794 AN XY: 74316

African (AFR) AF: 0.223 AC: 9234 AN: 41486

American (AMR) AF: 0.107 AC: 1640 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 309 AN: 3472

East Asian (EAS) AF: 0.218 AC: 1125 AN: 5154

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4806

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6833 AN: 67990

Other (OTH) AF: 0.136 AC: 286 AN: 2106

Alfa AF: 0.111 Hom.: 1714

Bravo AF: 0.147

Asia WGS AF: 0.231 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.10
DANN	Benign	0.84
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs723587; hg19: chr6-81056360;