chr17-49974408-C-T

Position:

• chr17-49974408-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLX4	NM_138281.3	c.*465C>T		3_prime_UTR_variant	3/3	ENST00000240306.5
DLX4	NM_001934.4	c.*465C>T		3_prime_UTR_variant	2/2
DLX4	XM_047435517.1	c.*465C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLX4	ENST00000240306.5	c.*465C>T		3_prime_UTR_variant	3/3	1	NM_138281.3	P1
DLX4	ENST00000411890.3	c.*465C>T		3_prime_UTR_variant	2/2	1
DLX4	ENST00000611342.1	c.*1058C>T		3_prime_UTR_variant	1/1
DLX4	ENST00000706528.1	n.2069C>T		non_coding_transcript_exon_variant	3/3

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

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.200

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

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.195

Alfa AF: 0.192 Hom.: 4433

Bravo AF: 0.204

Asia WGS AF: 0.234 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.46

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: rs1058564; hg19: chr17-48051772;