rs6976129

Variant names:

• chr7-27138127-C-T
• rs6976129
• NM_153631.3:c.-390+1956G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ENSG00000273433 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HOXA3	NM_153631.3	c.-390+1956G>A		intron_variant	Intron 2 of 5	ENST00000612286.5	NP_705895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA3	ENST00000612286.5	c.-390+1956G>A		intron_variant	Intron 2 of 5	2	NM_153631.3	ENSP00000484411.1

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

African (AFR) AF: 0.216 AC: 8937 AN: 41460

American (AMR) AF: 0.186 AC: 2848 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3468

East Asian (EAS) AF: 0.146 AC: 757 AN: 5176

South Asian (SAS) AF: 0.0672 AC: 323 AN: 4810

European-Finnish (FIN) AF: 0.130 AC: 1374 AN: 10592

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6151 AN: 68002

Other (OTH) AF: 0.119 AC: 250 AN: 2096

Alfa AF: 0.142 Hom.: 407

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
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs6976129; hg19: chr7-27177746;