rs4236167

Variant names:

• chr6-15533720-C-T
• rs4236167
• NM_032122.5:c.512-325G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-15533720-C-T
• chr6-15533720-C-A

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.512-325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 503,590 control chromosomes in the GnomAD database, including 60,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (15894 hom., cov: 33)
  • Exomes 𝑓: 0.50 (44821 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.13
• Publications: 15 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

LOC105374947 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-15533720-C-T is Benign according to our data. Variant chr6-15533720-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 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.512-325G>A		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.461-325G>A		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.407-325G>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.512-325G>A		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.407-325G>A		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.512-325G>A		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67622 AN: 152018 Hom.: 15887 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.498 AC: 174995 AN: 351454 Hom.: 44821 AF XY: 0.502 AC XY: 98764 AN XY: 196616

African (AFR) AF: 0.308 AC: 3258 AN: 10582

American (AMR) AF: 0.530 AC: 15119 AN: 28516

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 4709 AN: 12808

East Asian (EAS) AF: 0.640 AC: 8261 AN: 12916

South Asian (SAS) AF: 0.554 AC: 33239 AN: 59962

European-Finnish (FIN) AF: 0.622 AC: 9733 AN: 15652

Middle Eastern (MID) AF: 0.300 AC: 913 AN: 3042

European-Non Finnish (NFE) AF: 0.481 AC: 91538 AN: 190388

Other (OTH) AF: 0.468 AC: 8225 AN: 17588

GnomAD4 genome AF: 0.445 AC: 67655 AN: 152136 Hom.: 15894 Cov.: 33 AF XY: 0.455 AC XY: 33816 AN XY: 74360

African (AFR) AF: 0.312 AC: 12968 AN: 41498

American (AMR) AF: 0.465 AC: 7097 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3472

East Asian (EAS) AF: 0.616 AC: 3184 AN: 5170

South Asian (SAS) AF: 0.549 AC: 2648 AN: 4822

European-Finnish (FIN) AF: 0.629 AC: 6657 AN: 10576

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32395 AN: 68002

Other (OTH) AF: 0.411 AC: 868 AN: 2112

Alfa AF: 0.474 Hom.: 15752

Bravo AF: 0.427

Asia WGS AF: 0.578 AC: 2006 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	-0.92
CADD	Benign	0.24
DANN	Benign	0.63
PhyloP100		-2.1
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: rs4236167; hg19: chr6-15533951;