1-26432658-A-G

Variant names:

• chr1-26432658-A-G
• rs3811461
• NM_205861.3:c.-55-233A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_205861.3(DHDDS):​c.-55-233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 473,802 control chromosomes in the GnomAD database, including 25,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8596 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16458 hom.)
• Consequence: DHDDS NM_205861.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0140
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-26432658-A-G is Benign according to our data. Variant chr1-26432658-A-G is described in ClinVar as Benign. ClinVar VariationId is 1257348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205861.3. 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
	DHDDS	NM_205861.3	MANE Select	c.-55-233A>G		intron	N/A	NP_995583.1	Q86SQ9-1
	DHDDS	NM_024887.4		c.-55-233A>G		intron	N/A	NP_079163.2
	DHDDS	NM_001243564.2		c.-55-233A>G		intron	N/A	NP_001230493.1	Q86SQ9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDDS	ENST00000236342.12	TSL:1 MANE Select	c.-55-233A>G		intron	N/A	ENSP00000236342.7	Q86SQ9-1
	DHDDS	ENST00000526219.5	TSL:1	c.-55-233A>G		intron	N/A	ENSP00000434219.1	Q86SQ9-3
	DHDDS	ENST00000434391.6	TSL:1	n.-55-233A>G		intron	N/A	ENSP00000403529.2	Q5T0A0

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47004 AN: 151928 Hom.: 8593 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.282 AC: 90862 AN: 321756 Hom.: 16458 Cov.: 0 AF XY: 0.288 AC XY: 49284 AN XY: 171072

African (AFR) AF: 0.440 AC: 4153 AN: 9434

American (AMR) AF: 0.276 AC: 4022 AN: 14566

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 2008 AN: 9806

East Asian (EAS) AF: 0.755 AC: 14842 AN: 19652

South Asian (SAS) AF: 0.400 AC: 16435 AN: 41132

European-Finnish (FIN) AF: 0.244 AC: 3994 AN: 16362

Middle Eastern (MID) AF: 0.254 AC: 352 AN: 1386

European-Non Finnish (NFE) AF: 0.210 AC: 40087 AN: 191292

Other (OTH) AF: 0.274 AC: 4969 AN: 18126

GnomAD4 genome AF: 0.309 AC: 47031 AN: 152046 Hom.: 8596 Cov.: 32 AF XY: 0.314 AC XY: 23328 AN XY: 74322

African (AFR) AF: 0.446 AC: 18502 AN: 41460

American (AMR) AF: 0.291 AC: 4448 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 719 AN: 3470

East Asian (EAS) AF: 0.724 AC: 3744 AN: 5172

South Asian (SAS) AF: 0.426 AC: 2047 AN: 4810

European-Finnish (FIN) AF: 0.235 AC: 2479 AN: 10566

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14132 AN: 67976

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.250 Hom.: 7738

Bravo AF: 0.319

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		-0.014
PromoterAI		-0.0046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: -17

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

Other links and lift over

dbSNP: rs3811461; hg19: chr1-26759149;