rs34957925

Positions:

chr7-27171929-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_018951.4(HOXA10):c.1203G>A(p.Arg401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 1,614,060 control chromosomes in the GnomAD database, including 1,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.025 ( 73 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1029 hom. )

Consequence

HOXA10
NM_018951.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0840

Variant links:

Genes affected

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]

HOXA10 links:

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]

HOXA9 links:

HOXA10-HOXA9 (HGNC:):

HOXA10-HOXA9 links:

HOXA10-AS (HGNC:40281): (HOXA10 antisense RNA)

HOXA10-AS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-27171929-C-T is Benign according to our data. Variant chr7-27171929-C-T is described in ClinVar as [Benign]. Clinvar id is 3056353.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.084 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3823/152248) while in subpopulation NFE AF= 0.0394 (2677/68018). AF 95% confidence interval is 0.0381. There are 73 homozygotes in gnomad4. There are 1848 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3823 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HOXA10	NM_018951.4 linkuse as main transcript	c.1203G>A	p.Arg401=	synonymous_variant	2/2	ENST00000283921.5	NP_061824.3
HOXA10-HOXA9	NR_037940.1 linkuse as main transcript	n.617-6962G>A		intron_variant, non_coding_transcript_variant
HOXA10	NR_037939.2 linkuse as main transcript	n.461G>A		non_coding_transcript_exon_variant	2/2
HOXA10-AS	NR_046609.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA10	ENST00000283921.5 linkuse as main transcript	c.1203G>A	p.Arg401=	synonymous_variant	2/2	1	NM_018951.4	ENSP00000283921	P2	P31260-1
HOXA10-AS	ENST00000519935.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3822

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00705

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0210

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.0350

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0282

GnomAD3 exomes

AF:

0.0258

AC:

6490

AN:

251488

Hom.:

131

AF XY:

0.0266

AC XY:

3610

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.0157

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00647

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.0411

Gnomad OTH exome

AF:

0.0275

GnomAD4 exome

AF:

0.0349

AC:

51038

AN:

1461812

Hom.:

1029

Cov.:

AF XY:

0.0344

AC XY:

25008

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00535

Gnomad4 AMR exome

AF:

0.0166

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00769

Gnomad4 FIN exome

AF:

0.0298

Gnomad4 NFE exome

AF:

0.0410

Gnomad4 OTH exome

AF:

0.0292

GnomAD4 genome

AF:

0.0251

AC:

3823

AN:

152248

Hom.:

Cov.:

AF XY:

0.0248

AC XY:

1848

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00703

Gnomad4 AMR

AF:

0.0210

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.0350

Gnomad4 NFE

AF:

0.0394

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0322

Hom.:

Bravo

AF:

0.0242

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0385

EpiControl

AF:

0.0437

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HOXA10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over