NM_032122.5:c.511+24397A>T

Variant names:

• chr6-15568662-T-A
• rs2619533
• NM_032122.5:c.511+24397A>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+24397A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,152 control chromosomes in the GnomAD database, including 2,707 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 0.15 (2707 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.511+24397A>T		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+24397A>T		intron_variant	Intron 7 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23516 AN: 152034 Hom.: 2705 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.155 AC: 23554 AN: 152152 Hom.: 2707 Cov.: 32 AF XY: 0.152 AC XY: 11307 AN XY: 74400

African (AFR) AF: 0.318 AC: 13184 AN: 41434

American (AMR) AF: 0.149 AC: 2284 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3472

East Asian (EAS) AF: 0.0795 AC: 412 AN: 5180

South Asian (SAS) AF: 0.117 AC: 565 AN: 4826

European-Finnish (FIN) AF: 0.0541 AC: 574 AN: 10612

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5780 AN: 68004

Other (OTH) AF: 0.148 AC: 313 AN: 2116

Alfa AF: 0.113 Hom.: 198

Bravo AF: 0.170

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.82
PhyloP100		-0.93
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: rs2619533; hg19: chr6-15568893;