rs1047631

Variant names:

• chr6-15522870-T-C
• rs1047631
• NM_032122.5:c.*105A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-15522870-T-C
• chr6-15522870-T-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.*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
• Publications: 33 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=-0.86).
• BP6: Variant 6-15522870-T-C is Benign according to our data. Variant chr6-15522870-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.*105A>G		3_prime_UTR	Exon 10 of 10	NP_115498.2
	DTNBP1	NM_001271668.2		c.*105A>G		3_prime_UTR	Exon 9 of 9	NP_001258597.1	A6NFV8
	DTNBP1	NM_001271669.2		c.*105A>G		3_prime_UTR	Exon 8 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.*105A>G		3_prime_UTR	Exon 10 of 10	ENSP00000341680.6	Q96EV8-1
	DTNBP1	ENST00000622898.4	TSL:1	c.*105A>G		3_prime_UTR	Exon 8 of 8	ENSP00000481997.1	A0A087WYP9
	DTNBP1	ENST00000857317.1		c.*105A>G		3_prime_UTR	Exon 10 of 10	ENSP00000527376.1

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

African (AFR) AF: 0.184 AC: 6008 AN: 32696

American (AMR) AF: 0.0770 AC: 3409 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 2448 AN: 25884

East Asian (EAS) AF: 0.0183 AC: 723 AN: 39544

South Asian (SAS) AF: 0.151 AC: 12844 AN: 84798

European-Finnish (FIN) AF: 0.156 AC: 8038 AN: 51368

Middle Eastern (MID) AF: 0.118 AC: 564 AN: 4798

European-Non Finnish (NFE) AF: 0.150 AC: 163000 AN: 1089542

Other (OTH) AF: 0.137 AC: 8121 AN: 59308

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

African (AFR) AF: 0.186 AC: 7708 AN: 41518

American (AMR) AF: 0.107 AC: 1642 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.0177 AC: 92 AN: 5190

South Asian (SAS) AF: 0.146 AC: 705 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1696 AN: 10608

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10210 AN: 68030

Other (OTH) AF: 0.148 AC: 313 AN: 2114

Alfa AF: 0.143 Hom.: 3217

Bravo AF: 0.146

Asia WGS AF: 0.0750 AC: 261 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	-0.86
CADD	Benign	0.68
DANN	Benign	0.43
PhyloP100		0.054
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: rs1047631; hg19: chr6-15523101; COSMIC: COSV59040343; COSMIC: COSV59040343;