Variant 7-27199072-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000522.5(HOXA13):c.922+84G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 1,356,444 control chromosomes in the GnomAD database, including 571,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.92 ( 65093 hom., cov: 30)

Exomes 𝑓: 0.91 ( 506011 hom. )

Consequence

HOXA13
NM_000522.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

HOXA13 (HGNC:5102): (homeobox A13) 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. Expansion of a polyalanine tract in the encoded protein can cause hand-foot-uterus syndrome, also known as hand-foot-genital syndrome. [provided by RefSeq, Jul 2008]

HOXA13 links:

HOTTIP (HGNC:37461): (HOXA distal transcript antisense RNA) This gene produces a long RNA in antisense to the HOXA gene cluster. This transcript may regulate expression of HOXA genes in cis. This gene is upregulated in tumors and is implicated in the promotion of cell proliferation. [provided by RefSeq, Dec 2017]

HOTTIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-27199072-C-G is Benign according to our data. Variant chr7-27199072-C-G is described in ClinVar as [Benign]. Clinvar id is 1295094.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA13	NM_000522.5 linkuse as main transcript	c.922+84G>C		intron_variant		ENST00000649031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA13	ENST00000649031.1 linkuse as main transcript	c.922+84G>C		intron_variant			NM_000522.5	P1
HOTTIP	ENST00000421733.1 linkuse as main transcript	n.167+331C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.922

AC:

140177

AN:

151984

Hom.:

65044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.983

Gnomad AMI

AF:

0.836

Gnomad AMR

AF:

0.873

Gnomad ASJ

AF:

0.961

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.901

Gnomad FIN

AF:

0.893

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.928

GnomAD4 exome

AF:

0.915

AC:

1101477

AN:

1204342

Hom.:

506011

AF XY:

0.915

AC XY:

550796

AN XY:

601910

show subpopulations

Gnomad4 AFR exome

AF:

0.988

Gnomad4 AMR exome

AF:

0.855

Gnomad4 ASJ exome

AF:

0.957

Gnomad4 EAS exome

AF:

0.600

Gnomad4 SAS exome

AF:

0.919

Gnomad4 FIN exome

AF:

0.892

Gnomad4 NFE exome

AF:

0.926

Gnomad4 OTH exome

AF:

0.917

GnomAD4 genome

AF:

0.922

AC:

140286

AN:

152102

Hom.:

65093

Cov.:

AF XY:

0.917

AC XY:

68179

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.983

Gnomad4 AMR

AF:

0.872

Gnomad4 ASJ

AF:

0.961

Gnomad4 EAS

AF:

0.599

Gnomad4 SAS

AF:

0.901

Gnomad4 FIN

AF:

0.893

Gnomad4 NFE

AF:

0.925

Gnomad4 OTH

AF:

0.929

Alfa

AF:

0.923

Hom.:

8047

Bravo

AF:

0.922

Asia WGS

AF:

0.792

AC:

2757

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.82

CADD

Benign

DANN

Benign

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over