rs10259620

Positions:

• chr7-27162670-A-G
• chr7-27162670-A-T

Variant summary

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

The NM_152739.4(HOXA9):​c.*933T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 209,434 control chromosomes in the GnomAD database, including 56,481 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 0.72 (39752 hom., cov: 33)
  • Exomes 𝑓: 0.76 (16729 hom.)
• Consequence: HOXA9 NM_152739.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

Genes affected

HOXA9 (HGNC:5109): (homeobox A9) 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. This gene is highly similar to the abdominal-B (Abd-B) gene of Drosophila. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis. Read-through transcription exists between this gene and the upstream homeobox A10 (HOXA10) gene.[provided by RefSeq, Mar 2011]

HOXA10-HOXA9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA9	NM_152739.4	c.*933T>C		3_prime_UTR_variant	2/2	ENST00000343483.7	NP_689952.1
HOXA10-HOXA9	NR_037940.1	n.1878T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA9	ENST00000343483.7	c.*933T>C		3_prime_UTR_variant	2/2	1	NM_152739.4	ENSP00000343619	P1
HOXA9	ENST00000497089.1	n.1323T>C		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109242 AN: 152012 Hom.: 39732 Cov.: 33

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.751

GnomAD4 exome AF: 0.761 AC: 43616 AN: 57304 Hom.: 16729 Cov.: 0 AF XY: 0.764 AC XY: 20425 AN XY: 26744

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.693

Gnomad4 ASJ exome AF: 0.836

Gnomad4 EAS exome AF: 0.678

Gnomad4 SAS exome AF: 0.854

Gnomad4 FIN exome AF: 0.708

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 0.747

GnomAD4 genome AF: 0.719 AC: 109312 AN: 152130 Hom.: 39752 Cov.: 33 AF XY: 0.717 AC XY: 53296 AN XY: 74382

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.751

Alfa AF: 0.770 Hom.: 73302

Bravo AF: 0.708

Asia WGS AF: 0.733 AC: 2550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0040
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs10259620; hg19: chr7-27202289; COSMIC: COSV58656472; COSMIC: COSV58656472;