chr7-27199072-C-G

Variant names:

• chr7-27199072-C-G
• rs2071265
• NM_000522.5:c.922+84G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000522.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA13	NM_000522.5	MANE Select	c.922+84G>C		intron	N/A	NP_000513.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA13	ENST00000649031.1	MANE Select	c.922+84G>C		intron	N/A	ENSP00000497112.1	P31271
	HOTTIP	ENST00000814985.1		n.124C>G		non_coding_transcript_exon	Exon 1 of 2
	HOTTIP	ENST00000421733.1	TSL:5	n.167+331C>G		intron	N/A

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

African (AFR) AF: 0.988 AC: 26804 AN: 27126

American (AMR) AF: 0.855 AC: 25523 AN: 29850

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 19141 AN: 20004

East Asian (EAS) AF: 0.600 AC: 22792 AN: 37960

South Asian (SAS) AF: 0.919 AC: 62912 AN: 68446

European-Finnish (FIN) AF: 0.892 AC: 31961 AN: 35832

Middle Eastern (MID) AF: 0.971 AC: 4888 AN: 5032

European-Non Finnish (NFE) AF: 0.926 AC: 860336 AN: 928706

Other (OTH) AF: 0.917 AC: 47120 AN: 51386

GnomAD4 genome AF: 0.922 AC: 140286 AN: 152102 Hom.: 65093 Cov.: 30 AF XY: 0.917 AC XY: 68179 AN XY: 74318

African (AFR) AF: 0.983 AC: 40855 AN: 41542

American (AMR) AF: 0.872 AC: 13348 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3337 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3051 AN: 5096

South Asian (SAS) AF: 0.901 AC: 4329 AN: 4804

European-Finnish (FIN) AF: 0.893 AC: 9448 AN: 10584

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62905 AN: 67982

Other (OTH) AF: 0.929 AC: 1963 AN: 2114

Alfa AF: 0.923 Hom.: 8047

Bravo AF: 0.922

Asia WGS AF: 0.792 AC: 2757 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.56
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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