rs6976129

chr7-27138127-C-T

Variant summary

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

The NM_153631.3(HOXA3):c.-390+1956G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,094 control chromosomes in the GnomAD database, including 1,733 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 0.14 (1733 hom., cov: 33)
• Consequence: HOXA3 NM_153631.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

Genes affected

HOXA3 (HGNC:5104): (homeobox A3) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA3	NM_153631.3	c.-390+1956G>A		intron_variant		ENST00000612286.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA3	ENST00000612286.5	c.-390+1956G>A		intron_variant		2	NM_153631.3	P1
HOXA-AS3	ENST00000518848.5	n.172+7979C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20893 AN: 151976 Hom.: 1730 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0675

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.138 AC: 20917 AN: 152094 Hom.: 1733 Cov.: 33 AF XY: 0.138 AC XY: 10267 AN XY: 74340

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.0672

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0905

Gnomad4 OTH AF: 0.119

Alfa AF: 0.133 Hom.: 301

Bravo AF: 0.150

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.22
Dann	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6976129; hg19: chr7-27177746;