NM_032122.5:c.356-7C>T

Variant names:

• chr6-15615406-G-A
• rs3829893
• NM_032122.5:c.356-7C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032122.5(DTNBP1):​c.356-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,078 control chromosomes in the GnomAD database, including 21,374 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1860 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19514 hom.)
• Consequence: DTNBP1 NM_032122.5 splice_region, intron
• Scores: Splicing: ADA: 0.00007164
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.951
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-15615406-G-A is Benign according to our data. Variant chr6-15615406-G-A is described in ClinVar as Benign. ClinVar VariationId is 163302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032122.5. 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.356-7C>T		splice_region intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.305-7C>T		splice_region intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.251-7C>T		splice_region intron	N/A	NP_001258598.1	A0A087WYP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.356-7C>T		splice_region intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.251-7C>T		splice_region intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.356-7C>T		splice_region intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22341 AN: 152010 Hom.: 1860 Cov.: 32

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.0969

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.170 AC: 42558 AN: 250606 AF XY: 0.172

Gnomad AFR exome AF: 0.0842

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.301

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.159 AC: 231585 AN: 1460950 Hom.: 19514 Cov.: 32 AF XY: 0.161 AC XY: 116734 AN XY: 726814

African (AFR) AF: 0.0845 AC: 2829 AN: 33474

American (AMR) AF: 0.166 AC: 7442 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 7151 AN: 26116

East Asian (EAS) AF: 0.272 AC: 10812 AN: 39680

South Asian (SAS) AF: 0.172 AC: 14838 AN: 86236

European-Finnish (FIN) AF: 0.143 AC: 7573 AN: 53036

Middle Eastern (MID) AF: 0.283 AC: 1633 AN: 5764

European-Non Finnish (NFE) AF: 0.152 AC: 168718 AN: 1111554

Other (OTH) AF: 0.175 AC: 10589 AN: 60368

GnomAD4 genome AF: 0.147 AC: 22353 AN: 152128 Hom.: 1860 Cov.: 32 AF XY: 0.150 AC XY: 11152 AN XY: 74368

African (AFR) AF: 0.0842 AC: 3496 AN: 41524

American (AMR) AF: 0.171 AC: 2610 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1563 AN: 5184

South Asian (SAS) AF: 0.182 AC: 879 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1576 AN: 10574

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10721 AN: 67978

Other (OTH) AF: 0.188 AC: 398 AN: 2112

Alfa AF: 0.162 Hom.: 6764

Bravo AF: 0.144

Asia WGS AF: 0.224 AC: 781 AN: 3476

EpiCase AF: 0.173

EpiControl AF: 0.175

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.1
DANN	Benign	0.47
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000072
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.010		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: rs3829893; hg19: chr6-15615637; COSMIC: COSV59037366;