rs651922

Variant names:

• chr11-126331395-A-G
• rs651922
• NM_014026.6:c.377-10A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-126331395-A-G
• chr11-126331395-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014026.6(DCPS):​c.377-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,613,582 control chromosomes in the GnomAD database, including 51,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4569 hom., cov: 31)
  • Exomes 𝑓: 0.25 (46931 hom.)
• Consequence: DCPS NM_014026.6 intron
• Scores: Splicing: ADA: 0.00006390
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 22 publications found

Genes affected

DCPS (HGNC:29812): (decapping enzyme, scavenger) This gene encodes a member of the histidine triad family of pyrophosphatases that removes short mRNA fragments containing the 5′ mRNA cap structure, which appear in the 3′ → 5′ mRNA decay pathway, following deadenylation and exosome-mediated turnover. This enzyme hydrolyzes the triphosphate linkage of the cap structure (7-methylguanosine nucleoside triphosphate) to yield 7-methylguanosine monophosphate and nucleoside diphosphate. It protects the cell from the potentially toxic accumulation of these short, capped mRNA fragments, and regulates the activity of other cap-binding proteins, which are inhibited by their accumulation. It also acts as a transcript-specific modulator of pre-mRNA splicing and microRNA turnover. [provided by RefSeq, Apr 2017]

DCPS Gene-Disease associations (from GenCC):

• Al-Raqad syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCPS	NM_014026.6	c.377-10A>G		intron_variant	Intron 2 of 5	ENST00000263579.5	NP_054745.1
DCPS	NM_001350236.2	c.398-10A>G		intron_variant	Intron 2 of 5		NP_001337165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCPS	ENST00000263579.5	c.377-10A>G		intron_variant	Intron 2 of 5	1	NM_014026.6	ENSP00000263579.4
DCPS	ENST00000648516.1	c.98-10A>G		intron_variant	Intron 3 of 6			ENSP00000497684.1
DCPS	ENST00000530860.5	n.-9A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37155 AN: 151890 Hom.: 4565 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.244

GnomAD2 exomes AF: 0.242 AC: 60786 AN: 251048 AF XY: 0.240

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.176

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.251 AC: 366941 AN: 1461574 Hom.: 46931 Cov.: 33 AF XY: 0.250 AC XY: 181953 AN XY: 727088

African (AFR) AF: 0.218 AC: 7280 AN: 33468

American (AMR) AF: 0.273 AC: 12219 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6650 AN: 26102

East Asian (EAS) AF: 0.189 AC: 7512 AN: 39698

South Asian (SAS) AF: 0.214 AC: 18443 AN: 86234

European-Finnish (FIN) AF: 0.234 AC: 12513 AN: 53382

Middle Eastern (MID) AF: 0.155 AC: 894 AN: 5762

European-Non Finnish (NFE) AF: 0.258 AC: 286454 AN: 1111842

Other (OTH) AF: 0.248 AC: 14976 AN: 60380

GnomAD4 genome AF: 0.245 AC: 37179 AN: 152008 Hom.: 4569 Cov.: 31 AF XY: 0.242 AC XY: 17956 AN XY: 74308

African (AFR) AF: 0.223 AC: 9242 AN: 41452

American (AMR) AF: 0.264 AC: 4034 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 879 AN: 3462

East Asian (EAS) AF: 0.184 AC: 952 AN: 5170

South Asian (SAS) AF: 0.228 AC: 1097 AN: 4808

European-Finnish (FIN) AF: 0.239 AC: 2535 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17666 AN: 67930

Other (OTH) AF: 0.244 AC: 515 AN: 2110

Alfa AF: 0.250 Hom.: 16240

Bravo AF: 0.242

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.67
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000064
dbscSNV1_RF	Benign	0.0
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: rs651922; hg19: chr11-126201290; COSMIC: COSV55010985; COSMIC: COSV55010985;