dbSNP rs115681222: DHDDS:n.-119G>A (chr1-26432313-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The ENST00000434391.6(DHDDS):n.-119G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00999 in 152,330 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DHDDS
ENST00000434391.6 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.54

Publications

1 publications found

Variant links:

Genes affected

DHDDS (HGNC:20603): (dehydrodolichyl diphosphate synthase subunit) The protein encoded by this gene catalyzes cis-prenyl chain elongation to produce the polyprenyl backbone of dolichol, a glycosyl carrier lipid required for the biosynthesis of several classes of glycoproteins. Mutations in this gene are associated with retinitis pigmentosa type 59. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

DHDDS links:

DHDDS-AS1 (HGNC:40925): (DHDDS antisense RNA 1)

DHDDS-AS1 links:

LOC124903883 (HGNC:):

LOC124903883 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 1-26432313-G-A is Benign according to our data. Variant chr1-26432313-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 297070.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00999 (1522/152330) while in subpopulation AFR AF = 0.0347 (1443/41572). AF 95% confidence interval is 0.0332. There are 32 homozygotes in GnomAd4. There are 713 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434391.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DHDDS	NM_205861.3	MANE Select	c.-119G>A	upstream_gene	N/A	NP_995583.1	Q86SQ9-1
DHDDS	NM_024887.4		c.-119G>A	upstream_gene	N/A	NP_079163.2
DHDDS	NM_001243564.2		c.-119G>A	upstream_gene	N/A	NP_001230493.1	Q86SQ9-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DHDDS	ENST00000434391.6	TSL:1	n.-119G>A	non_coding_transcript_exon	Exon 1 of 9	ENSP00000403529.2	Q5T0A0
DHDDS	ENST00000434391.6	TSL:1	n.-119G>A	5_prime_UTR	Exon 1 of 9	ENSP00000403529.2	Q5T0A0
DHDDS-AS1	ENST00000746082.1		n.462-1195C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00999

AC:

1521

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0348

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00621

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

506

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

516

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.00999

AC:

1522

AN:

152330

Hom.:

Cov.:

AF XY:

0.00957

AC XY:

713

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0347

AC:

1443

AN:

41572

American (AMR)

AF:

0.00386

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00347

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

4.5

PromoterAI

-0.22

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over