7-27165663-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001433944.1(HOXA10-HOXA9):​c.11-696T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 536,476 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 35)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: HOXA10-HOXA9 NM_001433944.1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

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.11-696T>A		intron	N/A	NP_001420873.1	D6RAR5
	HOXA9	NM_152739.4	MANE Select	c.-206T>A		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>A		intron	N/A	ENSP00000421799.3
	HOXA9	ENST00000465941.1	TSL:1	n.480-1822T>A		intron	N/A
	HOXA9	ENST00000497089.1	TSL:1	n.152-1822T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000186 AC: 1 AN: 536476 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 274956

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10856

American (AMR) AF: 0.00 AC: 0 AN: 12326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13220

East Asian (EAS) AF: 0.00 AC: 0 AN: 26498

South Asian (SAS) AF: 0.00 AC: 0 AN: 42032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2104

European-Non Finnish (NFE) AF: 0.00000269 AC: 1 AN: 372056

Other (OTH) AF: 0.00 AC: 0 AN: 28300

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.90
PhyloP100		2.2
PromoterAI		0.027	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

Other links and lift over

dbSNP: rs3801776; hg19: chr7-27205282;