rs6943542

Variant names:

• chr7-27129998-T-C
• rs6943542
• NM_153631.3:c.-389-2928A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-27129998-T-C
• chr7-27129998-T-A
• chr7-27129998-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153631.3(HOXA3):​c.-389-2928A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 1,199,474 control chromosomes in the GnomAD database, including 558,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68780 hom., cov: 35)
  • Exomes 𝑓: 0.97 (489780 hom.)
• Consequence: HOXA3 NM_153631.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82
• Publications: 1 publications found

Genes affected

HOXA3 (HGNC:5104): (homeobox A3) 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. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HOXA4 (HGNC:5105): (homeobox A4) 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. [provided by RefSeq, Jul 2008]

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

ENSG00000273433 (HGNC:):

HOXA-AS2 (HGNC:43745): (HOXA cluster antisense RNA 2) This gene produces a long non-coding RNA that promotes cell proliferation. This transcript may interact with enhancer of zeste homolog 2 Polycomb repressive complex to repress gene expression. [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=-0.58).
• BP6: Variant 7-27129998-T-C is Benign according to our data. Variant chr7-27129998-T-C is described in ClinVar as Benign. ClinVar VariationId is 1268576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153631.3. 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
	HOXA3	NM_153631.3	MANE Select	c.-389-2928A>G		intron	N/A	NP_705895.1	O43365
	HOXA4	NM_002141.5	MANE Select	c.616+120A>G		intron	N/A	NP_002132.3
	HOXA3	NM_001384335.1		c.-505-2928A>G		intron	N/A	NP_001371264.1	O43365

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA3	ENST00000612286.5	TSL:2 MANE Select	c.-389-2928A>G		intron	N/A	ENSP00000484411.1	O43365
	HOXA4	ENST00000360046.10	TSL:1 MANE Select	c.616+120A>G		intron	N/A	ENSP00000353151.5	Q00056
	HOXA4	ENST00000610970.1	TSL:1	c.616+120A>G		intron	N/A	ENSP00000479166.1	Q00056

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144523 AN: 152160 Hom.: 68722 Cov.: 35

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.933

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.946

GnomAD4 exome AF: 0.967 AC: 1012658 AN: 1047196 Hom.: 489780 Cov.: 13 AF XY: 0.966 AC XY: 509411 AN XY: 527570

African (AFR) AF: 0.899 AC: 21584 AN: 24004

American (AMR) AF: 0.970 AC: 31299 AN: 32258

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 20089 AN: 20510

East Asian (EAS) AF: 0.997 AC: 32287 AN: 32374

South Asian (SAS) AF: 0.937 AC: 65213 AN: 69596

European-Finnish (FIN) AF: 0.962 AC: 30461 AN: 31664

Middle Eastern (MID) AF: 0.959 AC: 4224 AN: 4404

European-Non Finnish (NFE) AF: 0.970 AC: 763703 AN: 786938

Other (OTH) AF: 0.964 AC: 43798 AN: 45448

GnomAD4 genome AF: 0.950 AC: 144641 AN: 152278 Hom.: 68780 Cov.: 35 AF XY: 0.949 AC XY: 70617 AN XY: 74438

African (AFR) AF: 0.901 AC: 37462 AN: 41576

American (AMR) AF: 0.967 AC: 14810 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 3410 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5127 AN: 5136

South Asian (SAS) AF: 0.945 AC: 4562 AN: 4830

European-Finnish (FIN) AF: 0.957 AC: 10166 AN: 10620

Middle Eastern (MID) AF: 0.928 AC: 271 AN: 292

European-Non Finnish (NFE) AF: 0.970 AC: 65948 AN: 68010

Other (OTH) AF: 0.947 AC: 2003 AN: 2116

Alfa AF: 0.958 Hom.: 9011

Bravo AF: 0.948

Asia WGS AF: 0.968 AC: 3367 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	-0.58
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		1.8
PromoterAI		-0.018	Neutral
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: rs6943542; hg19: chr7-27169617;