7-27156494-C-T

Variant names:

• chr7-27156494-C-T
• rs2301721
• NM_006896.4:c.52G>A

Variant summary

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

The NM_006896.4(HOXA7):​c.52G>A​(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,596,288 control chromosomes in the GnomAD database, including 529,356 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.65 (37874 hom., cov: 35)
  • Exomes 𝑓: 0.82 (491482 hom.)
• Consequence: HOXA7 NM_006896.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8064014E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA7	NM_006896.4	c.52G>A	p.Ala18Thr	missense_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.52G>A	p.Ala18Thr	missense_variant	Exon 1 of 2	1	NM_006896.4	ENSP00000242159.3
HOXA7	ENST00000519842.1	c.52G>A	p.Ala18Thr	missense_variant	Exon 3 of 3	3		ENSP00000428563.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98284 AN: 152106 Hom.: 37875 Cov.: 35

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.692

GnomAD2 exomes AF: 0.773 AC: 188237 AN: 243600 AF XY: 0.788

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.684

Gnomad ASJ exome AF: 0.869

Gnomad EAS exome AF: 0.865

Gnomad FIN exome AF: 0.806

Gnomad NFE exome AF: 0.841

Gnomad OTH exome AF: 0.795

GnomAD4 exome AF: 0.818 AC: 1181243 AN: 1444064 Hom.: 491482 Cov.: 43 AF XY: 0.820 AC XY: 587226 AN XY: 715954

Gnomad4 AFR exome AF: 0.167 AC: 5460 AN: 32642

Gnomad4 AMR exome AF: 0.681 AC: 29456 AN: 43240

Gnomad4 ASJ exome AF: 0.866 AC: 22093 AN: 25520

Gnomad4 EAS exome AF: 0.854 AC: 33610 AN: 39338

Gnomad4 SAS exome AF: 0.822 AC: 69702 AN: 84832

Gnomad4 FIN exome AF: 0.814 AC: 43073 AN: 52914

Gnomad4 NFE exome AF: 0.841 AC: 925847 AN: 1100274

Gnomad4 Remaining exome AF: 0.794 AC: 47350 AN: 59604

GnomAD4 genome AF: 0.646 AC: 98299 AN: 152224 Hom.: 37874 Cov.: 35 AF XY: 0.648 AC XY: 48234 AN XY: 74430

Gnomad4 AFR AF: 0.195 AC: 0.194907 AN: 0.194907

Gnomad4 AMR AF: 0.693 AC: 0.693228 AN: 0.693228

Gnomad4 ASJ AF: 0.863 AC: 0.862824 AN: 0.862824

Gnomad4 EAS AF: 0.849 AC: 0.849035 AN: 0.849035

Gnomad4 SAS AF: 0.820 AC: 0.819801 AN: 0.819801

Gnomad4 FIN AF: 0.805 AC: 0.805493 AN: 0.805493

Gnomad4 NFE AF: 0.841 AC: 0.841139 AN: 0.841139

Gnomad4 OTH AF: 0.693 AC: 0.692999 AN: 0.692999

Alfa AF: 0.782 Hom.: 189617

Bravo AF: 0.613

TwinsUK AF: 0.841 AC: 3117

ALSPAC AF: 0.845 AC: 3258

ESP6500AA AF: 0.210 AC: 924

ESP6500EA AF: 0.835 AC: 7180

ExAC AF: 0.767 AC: 93000

Asia WGS AF: 0.792 AC: 2755 AN: 3478

EpiCase AF: 0.843

EpiControl AF: 0.836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.069
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.50	T;T
MetaRNN	Benign	0.0000028	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.31	N;N
REVEL	Benign	0.021
Sift	Benign	0.33	T;.
Sift4G	Benign	0.44	T;.
Polyphen		0.080	B;.
Vest4		0.068
MPC		0.38
ClinPred		0.014	T
GERP RS		4.3
Varity_R		0.075
gMVP		0.48
Mutation Taster		=88/12	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

Publications

LitVar

Other links and lift over

dbSNP: rs2301721; hg19: chr7-27196113; COSMIC: COSV54216737; COSMIC: COSV54216737;