7-27129100-C-T

Position:

• chr7-27129100-C-T

Variant summary

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

The NM_002141.5(HOXA4):​c.*125G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 729,228 control chromosomes in the GnomAD database, including 337,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68802 hom., cov: 33)
  • Exomes 𝑓: 0.96 (268501 hom.)
• Consequence: HOXA4 NM_002141.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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]

ENSG00000273433 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 7-27129100-C-T is Benign according to our data. Variant chr7-27129100-C-T is described in ClinVar as [Benign]. Clinvar id is 1182927.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.*125G>A		3_prime_UTR_variant	2/2	ENST00000360046.10	NP_002132.3
HOXA3	NM_153631.3	c.-389-2030G>A		intron_variant		ENST00000612286.5	NP_705895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA4	ENST00000360046.10	c.*125G>A		3_prime_UTR_variant	2/2	1	NM_002141.5	ENSP00000353151.5
HOXA3	ENST00000612286.5	c.-389-2030G>A		intron_variant		2	NM_153631.3	ENSP00000484411.1

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144562 AN: 152190 Hom.: 68744 Cov.: 33

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: 0.927

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.946

GnomAD4 exome AF: 0.965 AC: 556484 AN: 576920 Hom.: 268501 Cov.: 5 AF XY: 0.963 AC XY: 299992 AN XY: 311490

Gnomad4 AFR exome AF: 0.897

Gnomad4 AMR exome AF: 0.972

Gnomad4 ASJ exome AF: 0.979

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.938

Gnomad4 FIN exome AF: 0.963

Gnomad4 NFE exome AF: 0.968

Gnomad4 OTH exome AF: 0.963

GnomAD4 genome AF: 0.950 AC: 144680 AN: 152308 Hom.: 68802 Cov.: 33 AF XY: 0.949 AC XY: 70658 AN XY: 74474

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.982

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.957

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.947

Alfa AF: 0.967 Hom.: 19957

Bravo AF: 0.948

Asia WGS AF: 0.968 AC: 3368 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	-0.42
CADD	Benign	13
DANN	Benign	0.93

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: rs4722662; hg19: chr7-27168719;