7-27129998-T-C

Position:

• chr7-27129998-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153631.3(HOXA3):​c.-389-2928A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 1,199,474 control chromosomes in the GnomAD database, including 558,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68780 hom., cov: 35)
  • Exomes 𝑓: 0.97 (489780 hom.)
• Consequence: HOXA3 NM_153631.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82

Genes affected

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]

HOXA4 (HGNC:5105): (homeobox A4) 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. [provided by RefSeq, Jul 2008]

HOXA-AS3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 7-27129998-T-C is Benign according to our data. Variant chr7-27129998-T-C is described in ClinVar as [Benign]. Clinvar id is 1268576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA3	NM_153631.3	c.-389-2928A>G		intron_variant		ENST00000612286.5	NP_705895.1
HOXA4	NM_002141.5	c.616+120A>G		intron_variant		ENST00000360046.10	NP_002132.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA3	ENST00000612286.5	c.-389-2928A>G		intron_variant		2	NM_153631.3	ENSP00000484411.1
HOXA4	ENST00000360046.10	c.616+120A>G		intron_variant		1	NM_002141.5	ENSP00000353151.5

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144523 AN: 152160 Hom.: 68722 Cov.: 35

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.933

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.946

GnomAD4 exome AF: 0.967 AC: 1012658 AN: 1047196 Hom.: 489780 Cov.: 13 AF XY: 0.966 AC XY: 509411 AN XY: 527570

Gnomad4 AFR exome AF: 0.899

Gnomad4 AMR exome AF: 0.970

Gnomad4 ASJ exome AF: 0.979

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.962

Gnomad4 NFE exome AF: 0.970

Gnomad4 OTH exome AF: 0.964

GnomAD4 genome AF: 0.950 AC: 144641 AN: 152278 Hom.: 68780 Cov.: 35 AF XY: 0.949 AC XY: 70617 AN XY: 74438

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.982

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.957

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.947

Alfa AF: 0.960 Hom.: 8702

Bravo AF: 0.948

Asia WGS AF: 0.968 AC: 3367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.76

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: rs6943542; hg19: chr7-27169617;