rs4715988

Variant names:

• chr6-15617878-C-T
• rs4715988
• NM_032122.5:c.356-2479G>A

Variant summary

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

The NM_032122.5(DTNBP1):​c.356-2479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,818 control chromosomes in the GnomAD database, including 24,149 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 0.55 (24149 hom., cov: 31)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.356-2479G>A		intron_variant	Intron 5 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.356-2479G>A		intron_variant	Intron 5 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84065 AN: 151700 Hom.: 24119 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.554 AC: 84145 AN: 151818 Hom.: 24149 Cov.: 31 AF XY: 0.544 AC XY: 40366 AN XY: 74180

African (AFR) AF: 0.686 AC: 28412 AN: 41426

American (AMR) AF: 0.535 AC: 8153 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2199 AN: 3466

East Asian (EAS) AF: 0.384 AC: 1982 AN: 5162

South Asian (SAS) AF: 0.447 AC: 2150 AN: 4806

European-Finnish (FIN) AF: 0.370 AC: 3878 AN: 10492

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35498 AN: 67902

Other (OTH) AF: 0.589 AC: 1241 AN: 2106

Alfa AF: 0.537 Hom.: 2958

Bravo AF: 0.572

Asia WGS AF: 0.423 AC: 1474 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-0.64
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: rs4715988; hg19: chr6-15618109;