chr7-27183944-G-T

Variant names:

• chr7-27183944-G-T
• rs6968828
• NM_005523.6:c.709+492C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005523.6(HOXA11):​c.709+492C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,964 control chromosomes in the GnomAD database, including 22,133 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22133 hom., cov: 32)
• Consequence: HOXA11 NM_005523.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• Publications: 14 publications found

Genes affected

HOXA11 (HGNC:5101): (homeobox A11) 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. This gene is involved in the regulation of uterine development and is required for female fertility. Mutations in this gene can cause radio-ulnar synostosis with amegakaryocytic thrombocytopenia. [provided by RefSeq, Jul 2008]

HOXA11 Gene-Disease associations (from GenCC):

• radioulnar synostosis with amegakaryocytic thrombocytopenia 1

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000293630 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005523.6. 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
	HOXA11	NM_005523.6	MANE Select	c.709+492C>A		intron	N/A	NP_005514.1	P31270

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA11	ENST00000006015.4	TSL:1 MANE Select	c.709+492C>A		intron	N/A	ENSP00000006015.3	P31270
	HOXA11	ENST00000517402.1	TSL:1	c.616+492C>A		intron	N/A	ENSP00000448962.1	H0YIA6
	ENSG00000293630	ENST00000716621.1		n.382-4657G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81562 AN: 151846 Hom.: 22127 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81592 AN: 151964 Hom.: 22133 Cov.: 32 AF XY: 0.537 AC XY: 39879 AN XY: 74252

African (AFR) AF: 0.467 AC: 19364 AN: 41462

American (AMR) AF: 0.558 AC: 8531 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3470

East Asian (EAS) AF: 0.546 AC: 2798 AN: 5124

South Asian (SAS) AF: 0.561 AC: 2697 AN: 4808

European-Finnish (FIN) AF: 0.545 AC: 5754 AN: 10560

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38454 AN: 67948

Other (OTH) AF: 0.568 AC: 1197 AN: 2106

Alfa AF: 0.561 Hom.: 97524

Bravo AF: 0.538

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.93
PhyloP100		3.4
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: rs6968828; hg19: chr7-27223563;