rs1859164

Positions:

• chr7-27178800-T-C
• chr7-27178800-T-G

Variant summary

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

The ENST00000396344.4(HOXA10):​c.10+846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,032 control chromosomes in the GnomAD database, including 12,643 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 0.39 (12643 hom., cov: 33)
• Consequence: HOXA10 ENST00000396344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

HOXA10 (HGNC:5100): (homeobox A10) 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 that may regulate gene expression, morphogenesis, and differentiation. More specifically, it may function in fertility, embryo viability, and regulation of hematopoietic lineage commitment. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the downstream homeobox A9 (HOXA9) 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA10-HOXA9	NR_037940.1	n.616+846A>G		intron_variant, non_coding_transcript_variant
HOXA10	NR_037939.2	n.216+846A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA10	ENST00000396344.4	c.10+846A>G		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59046 AN: 151912 Hom.: 12644 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.389 AC: 59068 AN: 152032 Hom.: 12643 Cov.: 33 AF XY: 0.389 AC XY: 28921 AN XY: 74334

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.435

Alfa AF: 0.284 Hom.: 770

Bravo AF: 0.377

Asia WGS AF: 0.484 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.61

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: rs1859164; hg19: chr7-27218419;