rs16876573

Variant names:

• chr6-15524467-T-C
• rs16876573
• ENST00000338950.9:c.870A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_183040.2(DTNBP1):​c.870A>G​(p.Pro290Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,613,570 control chromosomes in the GnomAD database, including 1,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (116 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1502 hom.)
• Consequence: DTNBP1 NM_183040.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.161
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-15524467-T-C is Benign according to our data. Variant chr6-15524467-T-C is described in ClinVar as Benign. ClinVar VariationId is 178772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.161 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183040.2. 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+59A>G		intron	N/A	NP_115498.2
	DTNBP1	NM_183040.2		c.870A>G	p.Pro290Pro	synonymous	Exon 9 of 9	NP_898861.1
	DTNBP1	NM_001271668.2		c.760+59A>G		intron	N/A	NP_001258597.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	ENST00000338950.9	TSL:1	c.870A>G	p.Pro290Pro	synonymous	Exon 9 of 9	ENSP00000344718.5
	DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.811+59A>G		intron	N/A	ENSP00000341680.6
	DTNBP1	ENST00000622898.4	TSL:1	c.706+59A>G		intron	N/A	ENSP00000481997.1

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4870 AN: 152142 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0397

GnomAD2 exomes AF: 0.0356 AC: 8944 AN: 251342 AF XY: 0.0389

Gnomad AFR exome AF: 0.0178

Gnomad AMR exome AF: 0.0229

Gnomad ASJ exome AF: 0.0342

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.0132

Gnomad NFE exome AF: 0.0426

Gnomad OTH exome AF: 0.0342

GnomAD4 exome AF: 0.0413 AC: 60398 AN: 1461310 Hom.: 1502 Cov.: 34 AF XY: 0.0422 AC XY: 30670 AN XY: 726820

African (AFR) AF: 0.0176 AC: 590 AN: 33472

American (AMR) AF: 0.0243 AC: 1088 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 882 AN: 26118

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39688

South Asian (SAS) AF: 0.0712 AC: 6143 AN: 86248

European-Finnish (FIN) AF: 0.0125 AC: 666 AN: 53408

Middle Eastern (MID) AF: 0.0527 AC: 304 AN: 5768

European-Non Finnish (NFE) AF: 0.0436 AC: 48408 AN: 1111524

Other (OTH) AF: 0.0383 AC: 2312 AN: 60370

GnomAD4 genome AF: 0.0321 AC: 4885 AN: 152260 Hom.: 116 Cov.: 32 AF XY: 0.0323 AC XY: 2407 AN XY: 74442

African (AFR) AF: 0.0185 AC: 770 AN: 41560

American (AMR) AF: 0.0341 AC: 522 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3468

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5160

South Asian (SAS) AF: 0.0693 AC: 334 AN: 4820

European-Finnish (FIN) AF: 0.0121 AC: 129 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0426 AC: 2899 AN: 68022

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0363 Hom.: 72

Bravo AF: 0.0319

Asia WGS AF: 0.0270 AC: 92 AN: 3478

EpiCase AF: 0.0458

EpiControl AF: 0.0481

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-0.16
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: rs16876573; hg19: chr6-15524698; COSMIC: COSV107430691; COSMIC: COSV107430691;