chr17-49970057-G-A

Variant names:

• chr17-49970057-G-A
• rs919089
• NM_138281.3:c.283+306G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_138281.3(DLX4):​c.283+306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,968 control chromosomes in the GnomAD database, including 34,284 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34284 hom., cov: 31)
• Consequence: DLX4 NM_138281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 2 publications found

Genes affected

DLX4 (HGNC:2917): (distal-less homeobox 4) Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. The DLX proteins are postulated to play a role in forebrain and craniofacial development. Three transcript variants have been described for this gene, however, the full length nature of one variant has not been described. Studies of the two splice variants revealed that one encoded isoform functions as a repressor of the beta-globin gene while the other isoform lacks that function. [provided by RefSeq, Jul 2008]

DLX4 Gene-Disease associations (from GenCC):

• orofacial cleft 15

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138281.3. 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
	DLX4	NM_138281.3	MANE Select	c.283+306G>A		intron	N/A	NP_612138.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX4	ENST00000240306.5	TSL:1 MANE Select	c.283+306G>A		intron	N/A	ENSP00000240306.3
	DLX4	ENST00000503410.1	TSL:4	n.207+306G>A		intron	N/A
	DLX4	ENST00000505318.2	TSL:3	n.422+306G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99945 AN: 151852 Hom.: 34268 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.685

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.658 AC: 99998 AN: 151968 Hom.: 34284 Cov.: 31 AF XY: 0.658 AC XY: 48874 AN XY: 74270

African (AFR) AF: 0.457 AC: 18922 AN: 41430

American (AMR) AF: 0.792 AC: 12106 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2495 AN: 3468

East Asian (EAS) AF: 0.756 AC: 3894 AN: 5148

South Asian (SAS) AF: 0.710 AC: 3415 AN: 4810

European-Finnish (FIN) AF: 0.695 AC: 7341 AN: 10568

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49529 AN: 67942

Other (OTH) AF: 0.687 AC: 1449 AN: 2110

Alfa AF: 0.703 Hom.: 23091

Bravo AF: 0.657

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.58
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: rs919089; hg19: chr17-48047421;