rs788172

Positions:

• chr2-172088710-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178120.5(DLX1):​c.*453G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 153,648 control chromosomes in the GnomAD database, including 15,079 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 0.41 (14952 hom., cov: 34)
  • Exomes 𝑓: 0.36 (127 hom.)
• Consequence: DLX1 NM_178120.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

Genes affected

DLX1 (HGNC:2914): (distal-less homeobox 1) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein is localized to the nucleus where it may function as a transcriptional regulator of signals from multiple TGF-{beta} superfamily members. The encoded protein may play a role in the control of craniofacial patterning and the differentiation and survival of inhibitory neurons in the forebrain. This gene is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 2. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX1	NM_178120.5	c.*453G>A		3_prime_UTR_variant	3/3	ENST00000361725.5	NP_835221.2
DLX1	NM_001038493.2	c.*631G>A		3_prime_UTR_variant	2/2		NP_001033582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX1	ENST00000361725.5	c.*453G>A		3_prime_UTR_variant	3/3	1	NM_178120.5	ENSP00000354478	P1
DLX1	ENST00000341900.6	c.*631G>A		3_prime_UTR_variant	2/2	1		ENSP00000341786
DLX1	ENST00000475989.2	n.1295G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62972 AN: 151820 Hom.: 14930 Cov.: 34

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.360 AC: 615 AN: 1710 Hom.: 127 Cov.: 0 AF XY: 0.340 AC XY: 323 AN XY: 950

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.415 AC: 63040 AN: 151938 Hom.: 14952 Cov.: 34 AF XY: 0.409 AC XY: 30396 AN XY: 74282

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.403

Alfa AF: 0.339 Hom.: 18945

Bravo AF: 0.425

Asia WGS AF: 0.331 AC: 1151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.9
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs788172; hg19: chr2-172953438; COSMIC: COSV59394344; COSMIC: COSV59394344;