7-27184152-C-T

Variant names:

• chr7-27184152-C-T
• rs7801581
• NM_005523.6:c.709+284G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_005523.6(HOXA11):​c.709+284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,934 control chromosomes in the GnomAD database, including 4,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4531 hom., cov: 32)
• Consequence: HOXA11 NM_005523.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.642
• Publications: 34 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, 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=-0.43).
• BP6: Variant 7-27184152-C-T is Benign according to our data. Variant chr7-27184152-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 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+284G>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+284G>A		intron	N/A	ENSP00000006015.3	P31270
	HOXA11	ENST00000517402.1	TSL:1	c.616+284G>A		intron	N/A	ENSP00000448962.1	H0YIA6
	ENSG00000293630	ENST00000716621.1		n.382-4449C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36333 AN: 151816 Hom.: 4531 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.239 AC: 36340 AN: 151934 Hom.: 4531 Cov.: 32 AF XY: 0.237 AC XY: 17582 AN XY: 74264

African (AFR) AF: 0.250 AC: 10361 AN: 41426

American (AMR) AF: 0.209 AC: 3197 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3470

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5170

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4822

European-Finnish (FIN) AF: 0.246 AC: 2587 AN: 10534

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16989 AN: 67924

Other (OTH) AF: 0.222 AC: 467 AN: 2102

Alfa AF: 0.228 Hom.: 2947

Bravo AF: 0.230

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.43
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		0.64
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: rs7801581; hg19: chr7-27223771;