7-27128893-C-G

Position:

• chr7-27128893-C-G

Variant summary

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

The NM_002141.5(HOXA4):​c.*332G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 350,990 control chromosomes in the GnomAD database, including 161,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68949 hom., cov: 32)
  • Exomes 𝑓: 0.96 (92394 hom.)
• Consequence: HOXA4 NM_002141.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29

Genes affected

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]

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-AS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-27128893-C-G is Benign according to our data. Variant chr7-27128893-C-G is described in ClinVar as [Benign]. Clinvar id is 1278464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA4	NM_002141.5	c.*332G>C		3_prime_UTR_variant	2/2	ENST00000360046.10	NP_002132.3
HOXA3	NM_153631.3	c.-389-1823G>C		intron_variant		ENST00000612286.5	NP_705895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA4	ENST00000360046.10	c.*332G>C		3_prime_UTR_variant	2/2	1	NM_002141.5	ENSP00000353151.5
HOXA3	ENST00000612286.5	c.-389-1823G>C		intron_variant		2	NM_153631.3	ENSP00000484411.1

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144705 AN: 152176 Hom.: 68888 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.946

GnomAD4 exome AF: 0.964 AC: 191577 AN: 198696 Hom.: 92394 Cov.: 0 AF XY: 0.962 AC XY: 100111 AN XY: 104030

Gnomad4 AFR exome AF: 0.899

Gnomad4 AMR exome AF: 0.964

Gnomad4 ASJ exome AF: 0.979

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.938

Gnomad4 FIN exome AF: 0.965

Gnomad4 NFE exome AF: 0.969

Gnomad4 OTH exome AF: 0.965

GnomAD4 genome AF: 0.951 AC: 144826 AN: 152294 Hom.: 68949 Cov.: 32 AF XY: 0.950 AC XY: 70742 AN XY: 74470

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.969

Gnomad4 ASJ AF: 0.982

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.959

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.947

Alfa AF: 0.967 Hom.: 3300

Bravo AF: 0.950

Asia WGS AF: 0.971 AC: 3377 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	-0.84
CADD	Benign	3.4
DANN	Benign	0.63

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: rs4722661; hg19: chr7-27168512;