rs983186

chr7-27149040-G-Achr7-27149040-G-C

Variant summary

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

The NM_153631.3(HOXA3):c.-494+3248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,216 control chromosomes in the GnomAD database, including 30,840 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 0.58 (30840 hom., cov: 34)
• Consequence: HOXA3 NM_153631.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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)

HOXA6 (HGNC:5107): (homeobox A6) 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. [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 = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA3	NM_153631.3	c.-494+3248C>T		intron_variant		ENST00000612286.5
HOXA-AS3	NR_038832.1	n.177-2535G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA3	ENST00000612286.5	c.-494+3248C>T		intron_variant		2	NM_153631.3	P1
HOXA-AS3	ENST00000518848.5	n.173-2535G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88675 AN: 152098 Hom.: 30841 Cov.: 34

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.583 AC: 88689 AN: 152216 Hom.: 30840 Cov.: 34 AF XY: 0.583 AC XY: 43410 AN XY: 74426

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.637

Alfa AF: 0.737 Hom.: 55376

Bravo AF: 0.556

Asia WGS AF: 0.665 AC: 2313 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	6.8
Dann	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs983186; hg19: chr7-27188659;