rs1047631

chr6-15522870-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032122.5(DTNBP1):c.*105A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,584,464 control chromosomes in the GnomAD database, including 17,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1836 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15384 hom.)
• Consequence: DTNBP1 NM_032122.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0540

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-15522870-T-C is Benign according to our data. Variant chr6-15522870-T-C is described in ClinVar as [Benign]. Clinvar id is 1253457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNBP1	NM_032122.5	c.*105A>G		3_prime_UTR_variant	10/10	ENST00000344537.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNBP1	ENST00000344537.10	c.*105A>G		3_prime_UTR_variant	10/10	1	NM_032122.5	P1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22804 AN: 152154 Hom.: 1836 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.143 AC: 205155 AN: 1432192 Hom.: 15384 Cov.: 25 AF XY: 0.143 AC XY: 102209 AN XY: 713722

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0770

Gnomad4 ASJ exome AF: 0.0946

Gnomad4 EAS exome AF: 0.0183

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.150 AC: 22818 AN: 152272 Hom.: 1836 Cov.: 33 AF XY: 0.148 AC XY: 11012 AN XY: 74460

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0931

Gnomad4 EAS AF: 0.0177

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.148

Alfa AF: 0.138 Hom.: 2117

Bravo AF: 0.146

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.68
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1047631; hg19: chr6-15523101; COSMIC: COSV59040343; COSMIC: COSV59040343;