chr17-49974408-C-T

Variant names:

• chr17-49974408-C-T
• rs1058564
• NM_138281.3:c.*465C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138281.3(DLX4):​c.*465C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,260 control chromosomes in the GnomAD database, including 3,464 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 0.21 (3456 hom., cov: 31)
  • Exomes 𝑓: 0.21 (8 hom.)
• Consequence: DLX4 NM_138281.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX4	NM_138281.3	MANE Select	c.*465C>T		3_prime_UTR	Exon 3 of 3	NP_612138.1	Q92988-1
	DLX4	NM_001934.4		c.*465C>T		3_prime_UTR	Exon 2 of 2	NP_001925.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX4	ENST00000240306.5	TSL:1 MANE Select	c.*465C>T		3_prime_UTR	Exon 3 of 3	ENSP00000240306.3	Q92988-1
	DLX4	ENST00000611342.2		n.1470C>T		non_coding_transcript_exon	Exon 1 of 1
	DLX4	ENST00000705772.1		n.*1092C>T		non_coding_transcript_exon	Exon 3 of 3	ENSP00000520982.1	A0ABJ7H8D3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31914 AN: 151714 Hom.: 3452 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.207 AC: 89 AN: 430 Hom.: 8 Cov.: 0 AF XY: 0.229 AC XY: 48 AN XY: 210

African (AFR) AF: 0.308 AC: 8 AN: 26

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4 AN: 26

East Asian (EAS) AF: 0.167 AC: 2 AN: 12

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.350 AC: 14 AN: 40

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.185 AC: 53 AN: 286

Other (OTH) AF: 0.200 AC: 6 AN: 30

GnomAD4 genome AF: 0.210 AC: 31930 AN: 151830 Hom.: 3456 Cov.: 31 AF XY: 0.211 AC XY: 15642 AN XY: 74210

African (AFR) AF: 0.237 AC: 9818 AN: 41384

American (AMR) AF: 0.137 AC: 2084 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1243 AN: 5156

South Asian (SAS) AF: 0.298 AC: 1429 AN: 4800

European-Finnish (FIN) AF: 0.207 AC: 2184 AN: 10538

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13854 AN: 67916

Other (OTH) AF: 0.195 AC: 409 AN: 2100

Alfa AF: 0.195 Hom.: 6233

Bravo AF: 0.204

Asia WGS AF: 0.234 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		0.059
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: rs1058564; hg19: chr17-48051772;