rs78899540

Positions:

• chr7-27141473-A-C

Variant summary

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

The NM_019102.4(HOXA5):​c.*362T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0383 in 206,864 control chromosomes in the GnomAD database, including 210 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 0.039 (154 hom., cov: 33)
  • Exomes 𝑓: 0.038 (56 hom.)
• Consequence: HOXA5 NM_019102.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.31

Genes affected

HOXA5 (HGNC:5106): (homeobox A5) 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. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis. [provided by RefSeq, Jul 2008]

HOXA3 (HGNC:5104): (homeobox A3) 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. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA5	NM_019102.4	c.*362T>G		3_prime_UTR_variant	2/2	ENST00000222726.4	NP_061975.2
HOXA3	NM_153631.3	c.-493-1287T>G		intron_variant		ENST00000612286.5	NP_705895.1
HOXA-AS3	NR_038832.1	n.176+934A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA5	ENST00000222726.4	c.*362T>G		3_prime_UTR_variant	2/2	1	NM_019102.4	ENSP00000222726	P1
HOXA3	ENST00000612286.5	c.-493-1287T>G		intron_variant		2	NM_153631.3	ENSP00000484411	P1
HOXA-AS3	ENST00000518848.5	n.173-10102A>C		intron_variant, non_coding_transcript_variant		4
HOXA-AS3	ENST00000521197.5	n.176+934A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5869 AN: 152192 Hom.: 154 Cov.: 33

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0585

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.0377 AC: 2055 AN: 54554 Hom.: 56 Cov.: 0 AF XY: 0.0372 AC XY: 1065 AN XY: 28600

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.0375

Gnomad4 ASJ exome AF: 0.0360

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0204

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.0461

Gnomad4 OTH exome AF: 0.0383

GnomAD4 genome AF: 0.0385 AC: 5866 AN: 152310 Hom.: 154 Cov.: 33 AF XY: 0.0360 AC XY: 2681 AN XY: 74472

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0265

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.0584

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0493 Hom.: 58

Bravo AF: 0.0401

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.86

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: rs78899540; hg19: chr7-27181092;