ENST00000338950.9:c.*176C>T

Variant names:

• chr6-15524249-G-A
• rs742106
• ENST00000338950.9:c.*176C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000338950.9(DTNBP1):​c.*176C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,583,464 control chromosomes in the GnomAD database, including 114,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9198 hom., cov: 32)
  • Exomes 𝑓: 0.38 (105070 hom.)
• Consequence: DTNBP1 ENST00000338950.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550
• Publications: 25 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), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-15524249-G-A is Benign according to our data. Variant chr6-15524249-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000338950.9. 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
	DTNBP1	NM_032122.5	MANE Select	c.811+277C>T		intron	N/A	NP_115498.2
	DTNBP1	NM_183040.2		c.*176C>T		3_prime_UTR	Exon 9 of 9	NP_898861.1	Q96EV8-2
	DTNBP1	NM_001271668.2		c.760+277C>T		intron	N/A	NP_001258597.1	A6NFV8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	ENST00000338950.9	TSL:1	c.*176C>T		3_prime_UTR	Exon 9 of 9	ENSP00000344718.5	Q96EV8-2
	DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.811+277C>T		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.706+277C>T		intron	N/A	ENSP00000481997.1	A0A087WYP9

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50076 AN: 151904 Hom.: 9185 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.317

GnomAD2 exomes AF: 0.407 AC: 89690 AN: 220256 AF XY: 0.406

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.562

Gnomad FIN exome AF: 0.415

Gnomad NFE exome AF: 0.364

Gnomad OTH exome AF: 0.387

GnomAD4 exome AF: 0.378 AC: 541410 AN: 1431442 Hom.: 105070 Cov.: 48 AF XY: 0.381 AC XY: 270772 AN XY: 711082

African (AFR) AF: 0.174 AC: 5732 AN: 32880

American (AMR) AF: 0.508 AC: 21247 AN: 41794

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 7942 AN: 25540

East Asian (EAS) AF: 0.561 AC: 21439 AN: 38226

South Asian (SAS) AF: 0.468 AC: 39425 AN: 84214

European-Finnish (FIN) AF: 0.413 AC: 19842 AN: 47998

Middle Eastern (MID) AF: 0.296 AC: 1200 AN: 4060

European-Non Finnish (NFE) AF: 0.367 AC: 402838 AN: 1097782

Other (OTH) AF: 0.369 AC: 21745 AN: 58948

GnomAD4 genome AF: 0.330 AC: 50101 AN: 152022 Hom.: 9198 Cov.: 32 AF XY: 0.340 AC XY: 25244 AN XY: 74298

African (AFR) AF: 0.179 AC: 7421 AN: 41478

American (AMR) AF: 0.436 AC: 6665 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3472

East Asian (EAS) AF: 0.559 AC: 2885 AN: 5162

South Asian (SAS) AF: 0.470 AC: 2266 AN: 4820

European-Finnish (FIN) AF: 0.415 AC: 4377 AN: 10544

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24245 AN: 67960

Other (OTH) AF: 0.317 AC: 666 AN: 2100

Alfa AF: 0.351 Hom.: 18750

Bravo AF: 0.325

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.87
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs742106;

hg19: chr6-15524480;