9-214706-G-C

Variant names:

• chr9-214706-G-C
• rs540473
• XM_047423927.1:c.-152+3390G>C

Variant summary

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

The NR_160804.1(DOCK8-AS1):​n.1045C>G 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 0.452 in 1,555,630 control chromosomes in the GnomAD database, including 161,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17266 hom., cov: 34)
  • Exomes 𝑓: 0.45 (144520 hom.)
• Consequence: DOCK8-AS1 NR_160804.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.960
• Publications: 31 publications found

Genes affected

DOCK8 (HGNC:19191): (dedicator of cytokinesis 8) This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010]

DOCK8-AS1 (HGNC:26436): (DOCK8 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.3728811E-6).
• BP6: Variant 9-214706-G-C is Benign according to our data. Variant chr9-214706-G-C is described in ClinVar as Benign. ClinVar VariationId is 1224206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_160804.1. 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
	DOCK8-AS1	NR_160804.1		n.1045C>G		non_coding_transcript_exon	Exon 1 of 1
	DOCK8	NM_203447.4	MANE Select	c.-271G>C		upstream_gene	N/A	NP_982272.2	Q8NF50-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK8-AS1	ENST00000382387.4	TSL:6	n.1188C>G		non_coding_transcript_exon	Exon 1 of 1
	DOCK8-AS1	ENST00000648587.1		n.1036C>G		non_coding_transcript_exon	Exon 1 of 1
	DOCK8	ENST00000432829.7	TSL:1 MANE Select	c.-271G>C		upstream_gene	N/A	ENSP00000394888.3	Q8NF50-1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71816 AN: 151932 Hom.: 17246 Cov.: 34

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.502

GnomAD2 exomes AF: 0.496 AC: 75949 AN: 153120 AF XY: 0.496

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.572

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.726

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.439

Gnomad OTH exome AF: 0.490

GnomAD4 exome AF: 0.450 AC: 631301 AN: 1403586 Hom.: 144520 Cov.: 75 AF XY: 0.452 AC XY: 313192 AN XY: 693300

African (AFR) AF: 0.499 AC: 15795 AN: 31630

American (AMR) AF: 0.568 AC: 20557 AN: 36206

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10102 AN: 24826

East Asian (EAS) AF: 0.722 AC: 26012 AN: 36012

South Asian (SAS) AF: 0.526 AC: 42491 AN: 80794

European-Finnish (FIN) AF: 0.442 AC: 21330 AN: 48282

Middle Eastern (MID) AF: 0.485 AC: 2735 AN: 5636

European-Non Finnish (NFE) AF: 0.430 AC: 465013 AN: 1082120

Other (OTH) AF: 0.469 AC: 27266 AN: 58080

GnomAD4 genome AF: 0.473 AC: 71894 AN: 152044 Hom.: 17266 Cov.: 34 AF XY: 0.478 AC XY: 35494 AN XY: 74316

African (AFR) AF: 0.494 AC: 20524 AN: 41506

American (AMR) AF: 0.511 AC: 7818 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3468

East Asian (EAS) AF: 0.741 AC: 3812 AN: 5144

South Asian (SAS) AF: 0.524 AC: 2529 AN: 4822

European-Finnish (FIN) AF: 0.428 AC: 4521 AN: 10574

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29665 AN: 67922

Other (OTH) AF: 0.509 AC: 1075 AN: 2114

Alfa AF: 0.368 Hom.: 1799

Bravo AF: 0.487

TwinsUK AF: 0.413 AC: 1533

ALSPAC AF: 0.443 AC: 1709

ESP6500AA AF: 0.425 AC: 1470

ESP6500EA AF: 0.371 AC: 2548

ExAC AF: 0.413 AC: 40374

Asia WGS AF: 0.654 AC: 2269 AN: 3470

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_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.65
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.96
PROVEAN	Benign	3.3	N
REVEL	Benign	0.091
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.019
MPC		0.17
ClinPred		0.012	T
GERP RS		1.7
PromoterAI		0.11	Neutral
Varity_R		0.17
gMVP		0.0084
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: rs540473; hg19: chr9-214706; COSMIC: COSV66688138; COSMIC: COSV66688138;