rs2301720

Variant names:

• chr7-27156450-A-C
• rs2301720
• NM_006896.4:c.96T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006896.4(HOXA7):​c.96T>G​(p.Ala32Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 1,613,554 control chromosomes in the GnomAD database, including 588,711 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 0.79 (48027 hom., cov: 37)
  • Exomes 𝑓: 0.86 (540684 hom.)
• Consequence: HOXA7 NM_006896.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603
• Publications: 23 publications found

Genes affected

HOXA7 (HGNC:5108): (homeobox A7) 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. For example, the encoded protein represses the transcription of differentiation-specific genes during keratinocyte proliferation, but this repression is then overcome by differentiation signals. This gene is highly similar to the antennapedia (Antp) gene of Drosophila. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.603 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA7	NM_006896.4	c.96T>G	p.Ala32Ala	synonymous_variant	Exon 1 of 2	ENST00000242159.5	NP_008827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA7	ENST00000242159.5	c.96T>G	p.Ala32Ala	synonymous_variant	Exon 1 of 2	1	NM_006896.4	ENSP00000242159.3
HOXA7	ENST00000519842.1	c.*4T>G		downstream_gene_variant		3		ENSP00000428563.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119625 AN: 152150 Hom.: 48005 Cov.: 37

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.816

GnomAD2 exomes AF: 0.832 AC: 207706 AN: 249718 AF XY: 0.841

Gnomad AFR exome AF: 0.595

Gnomad AMR exome AF: 0.728

Gnomad ASJ exome AF: 0.924

Gnomad EAS exome AF: 0.866

Gnomad FIN exome AF: 0.820

Gnomad NFE exome AF: 0.870

Gnomad OTH exome AF: 0.849

GnomAD4 exome AF: 0.859 AC: 1254641 AN: 1461288 Hom.: 540684 Cov.: 58 AF XY: 0.860 AC XY: 625328 AN XY: 726856

African (AFR) AF: 0.605 AC: 20228 AN: 33452

American (AMR) AF: 0.728 AC: 32550 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 24065 AN: 26130

East Asian (EAS) AF: 0.855 AC: 33926 AN: 39662

South Asian (SAS) AF: 0.877 AC: 75642 AN: 86230

European-Finnish (FIN) AF: 0.827 AC: 44165 AN: 53392

Middle Eastern (MID) AF: 0.897 AC: 5170 AN: 5762

European-Non Finnish (NFE) AF: 0.870 AC: 967367 AN: 1111592

Other (OTH) AF: 0.853 AC: 51528 AN: 60382

GnomAD4 genome AF: 0.786 AC: 119696 AN: 152266 Hom.: 48027 Cov.: 37 AF XY: 0.785 AC XY: 58457 AN XY: 74446

African (AFR) AF: 0.612 AC: 25433 AN: 41542

American (AMR) AF: 0.765 AC: 11717 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3188 AN: 3472

East Asian (EAS) AF: 0.852 AC: 4392 AN: 5156

South Asian (SAS) AF: 0.880 AC: 4251 AN: 4830

European-Finnish (FIN) AF: 0.816 AC: 8656 AN: 10604

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59222 AN: 68032

Other (OTH) AF: 0.817 AC: 1728 AN: 2116

Alfa AF: 0.840 Hom.: 95032

Bravo AF: 0.770

Asia WGS AF: 0.865 AC: 3008 AN: 3478

EpiCase AF: 0.877

EpiControl AF: 0.870

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.60
PromoterAI		-0.060	Neutral
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: rs2301720; hg19: chr7-27196069; COSMIC: COSV54216726; COSMIC: COSV54216726;