ENST00000470747.5:c.11-696T>C

Variant names:

• chr7-27165663-A-G
• rs3801776
• ENST00000470747.5:c.11-696T>C

Variant summary

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

The ENST00000470747.5(HOXA10-HOXA9):​c.11-696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 687,948 control chromosomes in the GnomAD database, including 188,751 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 0.73 (40339 hom., cov: 35)
  • Exomes 𝑓: 0.74 (148412 hom.)
• Consequence: HOXA10-HOXA9 ENST00000470747.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 23 publications found

Genes affected

HOXA10-HOXA9 (HGNC:51908):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000470747.5. 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.11-696T>C		intron	N/A	NP_001420873.1	D6RAR5
	HOXA9	NM_152739.4	MANE Select	c.-206T>C		upstream_gene	N/A	NP_689952.1	P31269

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA10-HOXA9	ENST00000470747.5	TSL:3	c.11-696T>C		intron	N/A	ENSP00000421799.3
	HOXA9	ENST00000465941.1	TSL:1	n.480-1822T>C		intron	N/A
	HOXA9	ENST00000497089.1	TSL:1	n.152-1822T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110591 AN: 152126 Hom.: 40318 Cov.: 35

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.735

GnomAD4 exome AF: 0.743 AC: 397806 AN: 535704 Hom.: 148412 AF XY: 0.747 AC XY: 205025 AN XY: 274554

African (AFR) AF: 0.725 AC: 7859 AN: 10840

American (AMR) AF: 0.664 AC: 8177 AN: 12316

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 10210 AN: 13214

East Asian (EAS) AF: 0.677 AC: 17926 AN: 26486

South Asian (SAS) AF: 0.810 AC: 34004 AN: 41978

European-Finnish (FIN) AF: 0.696 AC: 20216 AN: 29062

Middle Eastern (MID) AF: 0.750 AC: 1578 AN: 2104

European-Non Finnish (NFE) AF: 0.746 AC: 277088 AN: 371436

Other (OTH) AF: 0.734 AC: 20748 AN: 28268

GnomAD4 genome AF: 0.727 AC: 110660 AN: 152244 Hom.: 40339 Cov.: 35 AF XY: 0.726 AC XY: 54018 AN XY: 74434

African (AFR) AF: 0.727 AC: 30189 AN: 41546

American (AMR) AF: 0.684 AC: 10470 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2695 AN: 3472

East Asian (EAS) AF: 0.637 AC: 3292 AN: 5168

South Asian (SAS) AF: 0.805 AC: 3891 AN: 4832

European-Finnish (FIN) AF: 0.685 AC: 7257 AN: 10598

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50537 AN: 68010

Other (OTH) AF: 0.735 AC: 1553 AN: 2114

Alfa AF: 0.739 Hom.: 50613

Bravo AF: 0.722

Asia WGS AF: 0.723 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.80
PhyloP100		2.2
PromoterAI		0.069	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3801776;

hg19: chr7-27205282;