rs3213654

chr7-97010056-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005222.4(DLX6):c.*9A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,581,382 control chromosomes in the GnomAD database, including 1,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (268 hom., cov: 32)
  • Exomes 𝑓: 0.012 (919 hom.)
• Consequence: DLX6 NM_005222.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.57

Genes affected

DLX6 (HGNC:2919): (distal-less homeobox 6) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. This family is comprised of at least 6 different members that encode proteins with roles in forebrain and craniofacial development. This gene is in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7. [provided by RefSeq, Jul 2008]

DLX6-AS1 (HGNC:37151): (DLX6 antisense RNA 1) Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-97010056-A-G is Benign according to our data. Variant chr7-97010056-A-G is described in ClinVar as [Benign]. Clinvar id is 1231769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLX6	NM_005222.4	c.*9A>G		3_prime_UTR_variant	3/3	ENST00000518156.3
DLX6-AS1	NR_015448.1	n.141+3869T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLX6	ENST00000518156.3	c.*9A>G		3_prime_UTR_variant	3/3	1	NM_005222.4	P1
DLX6-AS1	ENST00000430027.3	n.141+3869T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5648 AN: 152070 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.0772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000765

Gnomad OTH AF: 0.0377

GnomAD3 exomes AF: 0.0384 AC: 7521 AN: 195860 Hom.: 414 AF XY: 0.0354 AC XY: 3711 AN XY: 104934

Gnomad AFR exome AF: 0.0806

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.147

Gnomad SAS exome AF: 0.0480

Gnomad FIN exome AF: 0.000159

Gnomad NFE exome AF: 0.000438

Gnomad OTH exome AF: 0.0233

GnomAD4 exome AF: 0.0123 AC: 17627 AN: 1429194 Hom.: 919 Cov.: 32 AF XY: 0.0127 AC XY: 8964 AN XY: 707910

Gnomad4 AFR exome AF: 0.0761

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.000942

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.0460

Gnomad4 FIN exome AF: 0.000116

Gnomad4 NFE exome AF: 0.000227

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.0373 AC: 5683 AN: 152188 Hom.: 268 Cov.: 32 AF XY: 0.0397 AC XY: 2956 AN XY: 74422

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0517

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0128 Hom.: 88

Bravo AF: 0.0451

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	17
Dann	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs3213654; hg19: chr7-96639368; COSMIC: COSV50296566; COSMIC: COSV50296566;