chr7-97010056-A-G

Variant names:

• chr7-97010056-A-G
• rs3213654
• NM_005222.4:c.*9A>G

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.57
• Publications: 7 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=-0.49).
• BP6: Variant 7-97010056-A-G is Benign according to our data. Variant chr7-97010056-A-G is described in ClinVar as Benign. ClinVar VariationId is 1231769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 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.*9A>G		3_prime_UTR	Exon 3 of 3	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+3869T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	ENST00000518156.3	TSL:1 MANE Select	c.*9A>G		3_prime_UTR	Exon 3 of 3	ENSP00000428480.2
	DLX6-AS1	ENST00000458352.5	TSL:1	n.615+1769T>C		intron	N/A
	DLX6	ENST00000493273.2	TSL:3	n.1492A>G		non_coding_transcript_exon	Exon 3 of 3

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

GnomAD2 exomes AF: 0.0384 AC: 7521 AN: 195860 AF XY: 0.0354

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 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

African (AFR) AF: 0.0761 AC: 2486 AN: 32672

American (AMR) AF: 0.111 AC: 4330 AN: 38984

Ashkenazi Jewish (ASJ) AF: 0.000942 AC: 24 AN: 25472

East Asian (EAS) AF: 0.144 AC: 5438 AN: 37860

South Asian (SAS) AF: 0.0460 AC: 3783 AN: 82182

European-Finnish (FIN) AF: 0.000116 AC: 6 AN: 51524

Middle Eastern (MID) AF: 0.00506 AC: 29 AN: 5736

European-Non Finnish (NFE) AF: 0.000227 AC: 249 AN: 1095472

Other (OTH) AF: 0.0216 AC: 1282 AN: 59292

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

African (AFR) AF: 0.0772 AC: 3208 AN: 41536

American (AMR) AF: 0.0886 AC: 1355 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.141 AC: 726 AN: 5146

South Asian (SAS) AF: 0.0517 AC: 249 AN: 4814

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000765 AC: 52 AN: 67978

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0241 Hom.: 276

Bravo AF: 0.0451

Asia WGS AF: 0.130 AC: 451 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 04, 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	-0.49
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		2.6
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: rs3213654; hg19: chr7-96639368; COSMIC: COSV50296566; COSMIC: COSV50296566;