rs6656196

Variant names:

• chr1-26432282-G-A
• rs6656196
• ENST00000434391.6:n.-150G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-26432282-G-A
• chr1-26432282-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000434391.6(DHDDS):​n.-150G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,676 control chromosomes in the GnomAD database, including 8,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8592 hom., cov: 32)
  • Exomes 𝑓: 0.26 (30 hom.)
• Consequence: DHDDS ENST00000434391.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.217
• Publications: 8 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)

LOC124903883 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-26432282-G-A is Benign according to our data. Variant chr1-26432282-G-A is described in ClinVar as Benign. ClinVar VariationId is 297068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDDS	NM_205861.3	MANE Select	c.-150G>A		upstream_gene	N/A	NP_995583.1	Q86SQ9-1
	DHDDS	NM_024887.4		c.-150G>A		upstream_gene	N/A	NP_079163.2
	DHDDS	NM_001243564.2		c.-150G>A		upstream_gene	N/A	NP_001230493.1	Q86SQ9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDDS	ENST00000434391.6	TSL:1	n.-150G>A		non_coding_transcript_exon	Exon 1 of 9	ENSP00000403529.2	Q5T0A0
	DHDDS	ENST00000434391.6	TSL:1	n.-150G>A		5_prime_UTR	Exon 1 of 9	ENSP00000403529.2	Q5T0A0
	DHDDS-AS1	ENST00000746087.1		n.15C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47001 AN: 152020 Hom.: 8589 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.257 AC: 138 AN: 538 Hom.: 30 Cov.: 0 AF XY: 0.285 AC XY: 97 AN XY: 340

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.231 AC: 12 AN: 52

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 6 AN: 6

South Asian (SAS) AF: 0.410 AC: 50 AN: 122

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.198 AC: 68 AN: 344

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.309 AC: 47028 AN: 152138 Hom.: 8592 Cov.: 32 AF XY: 0.314 AC XY: 23328 AN XY: 74388

African (AFR) AF: 0.446 AC: 18516 AN: 41494

American (AMR) AF: 0.291 AC: 4451 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3726 AN: 5170

South Asian (SAS) AF: 0.424 AC: 2043 AN: 4814

European-Finnish (FIN) AF: 0.235 AC: 2489 AN: 10598

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

European-Non Finnish (NFE) AF: 0.208 AC: 14120 AN: 67982

Other (OTH) AF: 0.297 AC: 627 AN: 2114

Alfa AF: 0.258 Hom.: 1154

Bravo AF: 0.319

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		-0.22
PromoterAI		-0.15	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6656196; hg19: chr1-26758773; COSMIC: COSV52577791;