rs2743548

Variant names:

• chr6-15583593-A-C
• rs2743548
• NM_032122.5:c.511+9466T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-15583593-A-C
• chr6-15583593-A-G
• chr6-15583593-A-T

Variant summary

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

The NM_032122.5(DTNBP1):​c.511+9466T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,242 control chromosomes in the GnomAD database, including 1,468 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 0.12 (1468 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

DTNBP1 (HGNC:17328): (dystrobrevin binding protein 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and binds to alpha- and beta-dystrobrevins, which are components of the dystrophin-associated protein complex (DPC). Mutations in this gene are associated with Hermansky-Pudlak syndrome type 7. This gene may also be associated with schizophrenia. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNBP1 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.511+9466T>G		intron_variant	Intron 7 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.511+9466T>G		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18895 AN: 152124 Hom.: 1469 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0817

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.124 AC: 18914 AN: 152242 Hom.: 1468 Cov.: 32 AF XY: 0.123 AC XY: 9124 AN XY: 74456

African (AFR) AF: 0.219 AC: 9107 AN: 41520

American (AMR) AF: 0.134 AC: 2057 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0817 AC: 283 AN: 3464

East Asian (EAS) AF: 0.0794 AC: 412 AN: 5186

South Asian (SAS) AF: 0.112 AC: 539 AN: 4828

European-Finnish (FIN) AF: 0.0539 AC: 572 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0823 AC: 5597 AN: 68016

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.0992 Hom.: 128

Bravo AF: 0.135

Asia WGS AF: 0.107 AC: 370 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2743548; hg19: chr6-15583824;