7-27184536-C-A

Variant names:

• chr7-27184536-C-A
• rs553990793
• NM_005523.6:c.609G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_005523.6(HOXA11):​c.609G>T​(p.Thr203Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,499,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: HOXA11 NM_005523.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.290
• Publications: 1 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-AS (HGNC:24957): (HOXA11 antisense RNA) This gene produces a long non-coding RNA in antisense to transcription of the homeobox A11 gene. This transcript may associate with chromatin factors such as Polycomb repressive complex and act as a sponge for microRNAs, thereby participating in the regulation of expression of target genes. High levels of this transcript may be associated with tumor progression. [provided by RefSeq, Dec 2017]

ENSG00000293630 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.067).
• BP6: Variant 7-27184536-C-A is Benign according to our data. Variant chr7-27184536-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3050064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.29 with no splicing effect.
• BS2: High AC in GnomAd4 at 103 AD gene.

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.609G>T	p.Thr203Thr	synonymous	Exon 1 of 2	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.609G>T	p.Thr203Thr	synonymous	Exon 1 of 2	ENSP00000006015.3	P31270
	HOXA11	ENST00000517402.1	TSL:1	c.516G>T	p.Thr172Thr	synonymous	Exon 2 of 3	ENSP00000448962.1	H0YIA6
	HOXA11-AS	ENST00000520360.6	TSL:5	n.30C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.000686 AC: 104 AN: 151668 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000726 AC: 8 AN: 110232 AF XY: 0.0000821

Gnomad AFR exome AF: 0.00271

Gnomad AMR exome AF: 0.000106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000742 AC: 100 AN: 1347798 Hom.: 0 Cov.: 29 AF XY: 0.0000632 AC XY: 42 AN XY: 664778

African (AFR) AF: 0.00275 AC: 76 AN: 27666

American (AMR) AF: 0.0000980 AC: 3 AN: 30624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23884

East Asian (EAS) AF: 0.00 AC: 0 AN: 30692

South Asian (SAS) AF: 0.00 AC: 0 AN: 74520

European-Finnish (FIN) AF: 0.0000212 AC: 1 AN: 47110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4240

European-Non Finnish (NFE) AF: 0.00000475 AC: 5 AN: 1053460

Other (OTH) AF: 0.000270 AC: 15 AN: 55602

GnomAD4 genome AF: 0.000679 AC: 103 AN: 151774 Hom.: 0 Cov.: 32 AF XY: 0.000620 AC XY: 46 AN XY: 74168

African (AFR) AF: 0.00242 AC: 100 AN: 41406

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67870

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000451 Hom.: 0

Bravo AF: 0.000801

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	HOXA11-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		0.29

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: rs553990793; hg19: chr7-27224155; COSMIC: COSV107204403; COSMIC: COSV107204403;