chr7-27174938-T-C

Position:

• chr7-27174938-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000396344.4(HOXA10):​c.11-2765A>G variant causes a intron 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: HOXA10 ENST00000396344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

Genes affected

ENSG00000257184 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA10	NR_037939.2	n.217-2765A>G		intron_variant
HOXA10-HOXA9	NR_037940.1	n.616+4708A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000257184	ENST00000470747.4	c.10+4708A>G		intron_variant		3		ENSP00000421799.3
HOXA10	ENST00000396344.4	c.11-2765A>G		intron_variant		1		ENSP00000379633.4
HOXA9	ENST00000465941.1	n.243A>G		non_coding_transcript_exon_variant	1/2	1

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

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.462

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

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.423

Alfa AF: 0.437 Hom.: 11561

Bravo AF: 0.431

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.45

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: rs3779456; hg19: chr7-27214557;