6-15660640-T-C

Variant names:

• chr6-15660640-T-C
• rs909706
• NM_032122.5:c.56+2174A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032122.5(DTNBP1):​c.56+2174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 953,832 control chromosomes in the GnomAD database, including 194,169 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (33775 hom., cov: 31)
  • Exomes 𝑓: 0.63 (160394 hom.)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.922
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 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.56+2174A>G		intron	N/A	NP_115498.2
	DTNBP1	NM_001271668.2		c.56+2174A>G		intron	N/A	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.56+2174A>G		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.56+2174A>G		intron	N/A	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.56+2174A>G		intron	N/A	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000338950.9	TSL:1	c.56+2174A>G		intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100052 AN: 151924 Hom.: 33727 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.630 AC: 504740 AN: 801790 Hom.: 160394 AF XY: 0.626 AC XY: 252384 AN XY: 403132

African (AFR) AF: 0.802 AC: 14136 AN: 17622

American (AMR) AF: 0.546 AC: 14277 AN: 26144

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 8834 AN: 12428

East Asian (EAS) AF: 0.396 AC: 4395 AN: 11104

South Asian (SAS) AF: 0.543 AC: 35845 AN: 66000

European-Finnish (FIN) AF: 0.538 AC: 6335 AN: 11784

Middle Eastern (MID) AF: 0.721 AC: 1521 AN: 2110

European-Non Finnish (NFE) AF: 0.641 AC: 400492 AN: 624594

Other (OTH) AF: 0.630 AC: 18905 AN: 30004

GnomAD4 genome AF: 0.659 AC: 100155 AN: 152042 Hom.: 33775 Cov.: 31 AF XY: 0.649 AC XY: 48258 AN XY: 74304

African (AFR) AF: 0.786 AC: 32618 AN: 41480

American (AMR) AF: 0.603 AC: 9215 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2434 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2075 AN: 5172

South Asian (SAS) AF: 0.538 AC: 2592 AN: 4820

European-Finnish (FIN) AF: 0.533 AC: 5609 AN: 10532

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43380 AN: 67974

Other (OTH) AF: 0.679 AC: 1435 AN: 2112

Alfa AF: 0.673 Hom.: 20920

Bravo AF: 0.669

Asia WGS AF: 0.481 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.3
DANN	Benign	0.71
PhyloP100		0.92
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: rs909706; hg19: chr6-15660871;