rs3779456

Variant names:

• chr7-27174938-T-C
• rs3779456
• ENST00000465941.1:n.243A>G

Variant summary

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

The ENST00000465941.1(HOXA9):​n.243A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,676 control chromosomes in the GnomAD database, including 14,234 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 0.43 (14174 hom., cov: 33)
  • Exomes 𝑓: 0.39 (60 hom.)
• Consequence: HOXA9 ENST00000465941.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 12 publications found

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]

ENSG00000257184 (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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465941.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA10-HOXA9	NM_001433944.1		c.10+4708A>G		intron	N/A	NP_001420873.1
	HOXA10	NR_037939.2		n.217-2765A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA9	ENST00000465941.1	TSL:1	n.243A>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000257184	ENST00000470747.4	TSL:3	c.10+4708A>G		intron	N/A	ENSP00000421799.3
	HOXA10	ENST00000396344.4	TSL:1	c.11-2765A>G		intron	N/A	ENSP00000379633.4

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65111 AN: 151938 Hom.: 14171 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.394 AC: 244 AN: 620 Hom.: 60 Cov.: 0 AF XY: 0.383 AC XY: 134 AN XY: 350

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.534 AC: 47 AN: 88

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AF: 0.100 AC: 1 AN: 10

South Asian (SAS) AF: 0.385 AC: 10 AN: 26

European-Finnish (FIN) AF: 0.571 AC: 8 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.362 AC: 162 AN: 448

Other (OTH) AF: 0.462 AC: 12 AN: 26

GnomAD4 genome AF: 0.428 AC: 65148 AN: 152056 Hom.: 14174 Cov.: 33 AF XY: 0.430 AC XY: 31934 AN XY: 74326

African (AFR) AF: 0.412 AC: 17071 AN: 41466

American (AMR) AF: 0.503 AC: 7684 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1322 AN: 5154

South Asian (SAS) AF: 0.427 AC: 2058 AN: 4820

European-Finnish (FIN) AF: 0.444 AC: 4691 AN: 10568

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29548 AN: 67978

Other (OTH) AF: 0.423 AC: 893 AN: 2112

Alfa AF: 0.436 Hom.: 20171

Bravo AF: 0.431

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.45
PhyloP100		-1.6
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: rs3779456; hg19: chr7-27214557;