chr7-27173638-G-A

Position:

• chr7-27173638-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_018951.4(HOXA10):​c.669C>T​(p.Ala223=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00343 in 1,544,924 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (25 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (94 hom.)
• Consequence: HOXA10 NM_018951.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.69

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]

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]

HOXA10-HOXA9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-27173638-G-A is Benign according to our data. Variant chr7-27173638-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 865 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA10	NM_018951.4	c.669C>T	p.Ala223=	synonymous_variant	1/2	ENST00000283921.5
HOXA10-HOXA9	NR_037940.1	n.616+6008C>T		intron_variant, non_coding_transcript_variant
HOXA10	NR_037939.2	n.217-1465C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA10	ENST00000283921.5	c.669C>T	p.Ala223=	synonymous_variant	1/2	1	NM_018951.4	P2
HOXA10	ENST00000396344.4	c.11-1465C>T		intron_variant		1		A1
HOXA9	ENST00000465941.1	n.479+1064C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 865 AN: 152028 Hom.: 25 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00199

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00779 AC: 1102 AN: 141498 Hom.: 39 AF XY: 0.00701 AC XY: 537 AN XY: 76632

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000122

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000818

Gnomad FIN exome AF: 0.0686

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00318 AC: 4428 AN: 1392786 Hom.: 94 Cov.: 33 AF XY: 0.00302 AC XY: 2072 AN XY: 686804

Gnomad4 AFR exome AF: 0.0000966

Gnomad4 AMR exome AF: 0.000507

Gnomad4 ASJ exome AF: 0.0000800

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000775

Gnomad4 FIN exome AF: 0.0645

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.00265

GnomAD4 genome AF: 0.00569 AC: 865 AN: 152138 Hom.: 25 Cov.: 33 AF XY: 0.00817 AC XY: 608 AN XY: 74394

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0675

Gnomad4 NFE AF: 0.00199

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00193 Hom.: 0

Bravo AF: 0.000752

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HOXA10-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 13, 2019

This variant is classified as likely 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	-0.57
CADD	Benign	13
DANN	Benign	0.96

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: rs201128593; hg19: chr7-27213257;