NM_005222.4:c.437-85A>C

Variant names:

• chr7-97007553-A-C
• rs1207727
• NM_005222.4:c.437-85A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005222.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	NM_005222.4	MANE Select	c.437-85A>C		intron	N/A	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+6372T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	ENST00000518156.3	TSL:1 MANE Select	c.437-85A>C		intron	N/A	ENSP00000428480.2
	DLX6-AS1	ENST00000458352.5	TSL:1	n.615+4272T>G		intron	N/A
	DLX6	ENST00000555308.1	TSL:2	c.-33A>C		5_prime_UTR	Exon 1 of 2	ENSP00000451635.1

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

GnomAD2 exomes AF: 0.0530 AC: 8219 AN: 155208 AF XY: 0.0561

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 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

African (AFR) AF: 0.0127 AC: 335 AN: 26318

American (AMR) AF: 0.0348 AC: 1237 AN: 35566

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 748 AN: 23552

East Asian (EAS) AF: 0.000202 AC: 7 AN: 34730

South Asian (SAS) AF: 0.0795 AC: 5898 AN: 74200

European-Finnish (FIN) AF: 0.0449 AC: 2118 AN: 47152

Middle Eastern (MID) AF: 0.0594 AC: 308 AN: 5184

European-Non Finnish (NFE) AF: 0.0744 AC: 62684 AN: 842350

Other (OTH) AF: 0.0618 AC: 3055 AN: 49414

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

African (AFR) AF: 0.0128 AC: 533 AN: 41554

American (AMR) AF: 0.0449 AC: 687 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0756 AC: 364 AN: 4818

European-Finnish (FIN) AF: 0.0394 AC: 418 AN: 10610

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0702 AC: 4774 AN: 67990

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.6
DANN	Benign	0.82
PhyloP100		1.1
PromoterAI		-0.014	Neutral
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: rs1207727; hg19: chr7-96636865;