chr7-27129750-T-C

Position:

• chr7-27129750-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_153631.3(HOXA3):​c.-389-2680A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 152,234 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.031 (263 hom., cov: 33)
• Consequence: HOXA3 NM_153631.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.38

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]

ENSG00000273433 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 7-27129750-T-C is Benign according to our data. Variant chr7-27129750-T-C is described in ClinVar as [Benign]. Clinvar id is 1244153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA3	NM_153631.3	c.-389-2680A>G		intron_variant		ENST00000612286.5	NP_705895.1
HOXA4	NM_002141.5	c.617-179A>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.-389-2680A>G		intron_variant		2	NM_153631.3	ENSP00000484411.1
HOXA4	ENST00000360046.10	c.617-179A>G		intron_variant		1	NM_002141.5	ENSP00000353151.5

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4711 AN: 152116 Hom.: 257 Cov.: 33

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.0267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0311 AC: 4730 AN: 152234 Hom.: 263 Cov.: 33 AF XY: 0.0360 AC XY: 2679 AN XY: 74436

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.00288

Gnomad4 OTH AF: 0.0269

Alfa AF: 0.0237 Hom.: 96

Bravo AF: 0.0371

Asia WGS AF: 0.0810 AC: 279 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Benign	0.80

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: rs17449108; hg19: chr7-27169369;