rs11558324

Variant names:

• chr6-15662887-T-C
• rs11558324
• NM_032122.5:c.-18A>G

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.-18A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,603,324 control chromosomes in the GnomAD database, including 40,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3008 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37470 hom.)
• Consequence: DTNBP1 NM_032122.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.80
• Publications: 7 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=-0.78).
• BP6: Variant 6-15662887-T-C is Benign according to our data. Variant chr6-15662887-T-C is described in ClinVar as Benign. ClinVar VariationId is 262009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 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.-18A>G		5_prime_UTR	Exon 1 of 10	NP_115498.2
	DTNBP1	NM_001271668.2		c.-18A>G		5_prime_UTR	Exon 1 of 9	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.-18A>G		5_prime_UTR	Exon 1 of 8	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.-18A>G		5_prime_UTR	Exon 1 of 10	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.-18A>G		5_prime_UTR	Exon 1 of 8	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.-18A>G		5_prime_UTR	Exon 1 of 9	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28117 AN: 151922 Hom.: 3006 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.195

GnomAD2 exomes AF: 0.174 AC: 41003 AN: 235784 AF XY: 0.176

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.000506

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.218 AC: 316792 AN: 1451288 Hom.: 37470 Cov.: 34 AF XY: 0.215 AC XY: 155493 AN XY: 722508

African (AFR) AF: 0.127 AC: 4260 AN: 33420

American (AMR) AF: 0.132 AC: 5890 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 6860 AN: 26084

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39674

South Asian (SAS) AF: 0.0904 AC: 7792 AN: 86232

European-Finnish (FIN) AF: 0.157 AC: 6875 AN: 43810

Middle Eastern (MID) AF: 0.177 AC: 1021 AN: 5756

European-Non Finnish (NFE) AF: 0.245 AC: 271810 AN: 1111366

Other (OTH) AF: 0.203 AC: 12260 AN: 60260

GnomAD4 genome AF: 0.185 AC: 28127 AN: 152036 Hom.: 3008 Cov.: 32 AF XY: 0.177 AC XY: 13191 AN XY: 74326

African (AFR) AF: 0.130 AC: 5405 AN: 41486

American (AMR) AF: 0.165 AC: 2526 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5168

South Asian (SAS) AF: 0.0852 AC: 411 AN: 4824

European-Finnish (FIN) AF: 0.149 AC: 1581 AN: 10580

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16536 AN: 67904

Other (OTH) AF: 0.192 AC: 405 AN: 2108

Alfa AF: 0.212 Hom.: 738

Bravo AF: 0.186

Asia WGS AF: 0.0510 AC: 178 AN: 3470

ClinVar

ClinVar submissions

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	-0.78
CADD	Benign	6.1
DANN	Benign	0.85
PhyloP100		-1.8
PromoterAI		-0.074	Neutral
Mutation Taster		=300/0	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: rs11558324; hg19: chr6-15663118;