rs12525702

Variant names:

• chr6-15627540-C-T
• rs12525702
• NM_032122.5:c.223-65G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-15627540-C-T
• chr6-15627540-C-G

Variant summary

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

The NM_032122.5(DTNBP1):​c.223-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,602,088 control chromosomes in the GnomAD database, including 9,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (846 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9081 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.187
• 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), G2P, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-15627540-C-T is Benign according to our data. Variant chr6-15627540-C-T is described in ClinVar as Benign. ClinVar VariationId is 1282033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 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.223-65G>A		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.172-65G>A		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.118-65G>A		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.223-65G>A		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.118-65G>A		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.223-65G>A		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14160 AN: 151982 Hom.: 846 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.107 AC: 155824 AN: 1449988 Hom.: 9081 AF XY: 0.107 AC XY: 77480 AN XY: 721160

African (AFR) AF: 0.0185 AC: 615 AN: 33260

American (AMR) AF: 0.140 AC: 6138 AN: 43908

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5619 AN: 25910

East Asian (EAS) AF: 0.0439 AC: 1731 AN: 39424

South Asian (SAS) AF: 0.0616 AC: 5262 AN: 85384

European-Finnish (FIN) AF: 0.125 AC: 6223 AN: 49812

Middle Eastern (MID) AF: 0.197 AC: 1113 AN: 5660

European-Non Finnish (NFE) AF: 0.111 AC: 122396 AN: 1106646

Other (OTH) AF: 0.112 AC: 6727 AN: 59984

GnomAD4 genome AF: 0.0931 AC: 14161 AN: 152100 Hom.: 846 Cov.: 32 AF XY: 0.0944 AC XY: 7017 AN XY: 74340

African (AFR) AF: 0.0210 AC: 871 AN: 41508

American (AMR) AF: 0.136 AC: 2077 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3468

East Asian (EAS) AF: 0.0529 AC: 274 AN: 5178

South Asian (SAS) AF: 0.0596 AC: 287 AN: 4812

European-Finnish (FIN) AF: 0.133 AC: 1400 AN: 10564

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8068 AN: 67978

Other (OTH) AF: 0.126 AC: 266 AN: 2114

Alfa AF: 0.109 Hom.: 566

Bravo AF: 0.0901

Asia WGS AF: 0.0580 AC: 201 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	-0.73
CADD	Benign	6.5
DANN	Benign	0.78
PhyloP100		0.19
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: rs12525702; hg19: chr6-15627771;