rs1207727

Positions:

• chr7-97007553-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005222.4(DLX6):​c.437-85A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 1,290,700 control chromosomes in the GnomAD database, including 3,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (251 hom., cov: 33)
  • Exomes 𝑓: 0.067 (2847 hom.)
• Consequence: DLX6 NM_005222.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.12

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-97007553-A-C is Benign according to our data. Variant chr7-97007553-A-C is described in ClinVar as [Benign]. Clinvar id is 1225540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLX6	NM_005222.4	c.437-85A>C		intron_variant		ENST00000518156.3
DLX6-AS1	NR_015448.1	n.141+6372T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLX6	ENST00000518156.3	c.437-85A>C		intron_variant		1	NM_005222.4	P1
DLX6-AS1	ENST00000430027.3	n.141+6372T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7154 AN: 152116 Hom.: 251 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0435

GnomAD3 exomes AF: 0.0530 AC: 8219 AN: 155208 Hom.: 273 AF XY: 0.0561 AC XY: 4646 AN XY: 82794

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.0353

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.000271

Gnomad SAS exome AF: 0.0793

Gnomad FIN exome AF: 0.0449

Gnomad NFE exome AF: 0.0704

Gnomad OTH exome AF: 0.0520

GnomAD4 exome AF: 0.0671 AC: 76390 AN: 1138466 Hom.: 2847 Cov.: 16 AF XY: 0.0676 AC XY: 38775 AN XY: 573952

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.0348

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.0449

Gnomad4 NFE exome AF: 0.0744

Gnomad4 OTH exome AF: 0.0618

GnomAD4 genome AF: 0.0470 AC: 7155 AN: 152234 Hom.: 251 Cov.: 33 AF XY: 0.0453 AC XY: 3374 AN XY: 74422

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.0449

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0756

Gnomad4 FIN AF: 0.0394

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0531 Hom.: 47

Bravo AF: 0.0458

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.6
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: rs1207727; hg19: chr7-96636865;