rs1859164

Variant names:

• chr7-27178800-T-C
• rs1859164
• ENST00000470747.5:c.10+846A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001433944.1(HOXA10-HOXA9):​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-HOXA9 NM_001433944.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 6 publications found

Genes affected

HOXA10-HOXA9 (HGNC:51908):

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 Gene-Disease associations (from GenCC):

• female reproductive system disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000293630 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001433944.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA10-HOXA9	NM_001433944.1		c.10+846A>G		intron	N/A	NP_001420873.1	D6RAR5
	HOXA10	NR_037939.2		n.216+846A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA10-HOXA9	ENST00000470747.5	TSL:3	c.10+846A>G		intron	N/A	ENSP00000421799.3
	HOXA10	ENST00000396344.4	TSL:1	c.10+846A>G		intron	N/A	ENSP00000379633.4	P31260-2
	ENSG00000293630	ENST00000716621.1		n.382-9801T>C		intron	N/A

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

African (AFR) AF: 0.203 AC: 8425 AN: 41452

American (AMR) AF: 0.388 AC: 5930 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2753 AN: 5160

South Asian (SAS) AF: 0.499 AC: 2404 AN: 4822

European-Finnish (FIN) AF: 0.441 AC: 4656 AN: 10566

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31651 AN: 67952

Other (OTH) AF: 0.435 AC: 918 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1859164; hg19: chr7-27218419;