7-27199072-C-G

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56

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]

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]

ACMG classification

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	c.922+84G>C		intron_variant		ENST00000649031.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140177 AN: 151984 Hom.: 65044 Cov.: 30

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

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.: 30 AF XY: 0.917 AC XY: 68179 AN XY: 74318

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

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	12
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

Other links and lift over

dbSNP: rs2071265; hg19: chr7-27238691; COSMIC: COSV56084495; COSMIC: COSV56084495;