2-176105728-A-T

Variant names:

• chr2-176105728-A-T
• rs847148
• ENST00000498438.1:n.411+1102A>T

Variant summary

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

The ENST00000498438.1(HOXD11):​n.411+1102A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,034 control chromosomes in the GnomAD database, including 12,388 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 0.38 (12388 hom., cov: 32)
• Consequence: HOXD11 ENST00000498438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 4 publications found

Genes affected

HOXD11 (HGNC:5134): (homeobox D11) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD11	ENST00000498438.1	n.411+1102A>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57703 AN: 151916 Hom.: 12355 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.380 AC: 57788 AN: 152034 Hom.: 12388 Cov.: 32 AF XY: 0.372 AC XY: 27671 AN XY: 74316

African (AFR) AF: 0.578 AC: 23940 AN: 41450

American (AMR) AF: 0.373 AC: 5705 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1077 AN: 3470

East Asian (EAS) AF: 0.0642 AC: 331 AN: 5156

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4812

European-Finnish (FIN) AF: 0.285 AC: 3010 AN: 10578

Middle Eastern (MID) AF: 0.297 AC: 86 AN: 290

European-Non Finnish (NFE) AF: 0.319 AC: 21687 AN: 67964

Other (OTH) AF: 0.359 AC: 756 AN: 2108

Alfa AF: 0.230 Hom.: 540

Bravo AF: 0.398

Asia WGS AF: 0.214 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.83
PhyloP100		-0.021

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs847148; hg19: chr2-176970456;