7-27143527-A-G

Position:

• chr7-27143527-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_019102.4(HOXA5):​c.81T>C​(p.His27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,613,792 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (22 hom.)
• Consequence: HOXA5 NM_019102.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.81

Genes affected

HOXA5 (HGNC:5106): (homeobox A5) 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. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis. [provided by RefSeq, Jul 2008]

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]

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

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-27143527-A-G is Benign according to our data. Variant chr7-27143527-A-G is described in ClinVar as [Benign]. Clinvar id is 774314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.
• BS2: High AC in GnomAd4 at 534 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA5	NM_019102.4	c.81T>C	p.His27=	synonymous_variant	1/2	ENST00000222726.4	NP_061975.2
HOXA3	NM_153631.3	c.-493-3341T>C		intron_variant		ENST00000612286.5	NP_705895.1
HOXA-AS3	NR_038832.1	n.176+2988A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA5	ENST00000222726.4	c.81T>C	p.His27=	synonymous_variant	1/2	1	NM_019102.4	ENSP00000222726	P1
HOXA3	ENST00000612286.5	c.-493-3341T>C		intron_variant		2	NM_153631.3	ENSP00000484411	P1
HOXA-AS3	ENST00000518848.5	n.173-8048A>G		intron_variant, non_coding_transcript_variant		4
HOXA-AS3	ENST00000521197.5	n.176+2988A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 534 AN: 152212 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00462

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00392 AC: 975 AN: 248850 Hom.: 8 AF XY: 0.00387 AC XY: 521 AN XY: 134656

Gnomad AFR exome AF: 0.000432

Gnomad AMR exome AF: 0.00258

Gnomad ASJ exome AF: 0.0187

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000984

Gnomad FIN exome AF: 0.00444

Gnomad NFE exome AF: 0.00477

Gnomad OTH exome AF: 0.00541

GnomAD4 exome AF: 0.00410 AC: 5996 AN: 1461462 Hom.: 22 Cov.: 31 AF XY: 0.00405 AC XY: 2946 AN XY: 726990

Gnomad4 AFR exome AF: 0.000867

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.0181

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000917

Gnomad4 FIN exome AF: 0.00451

Gnomad4 NFE exome AF: 0.00429

Gnomad4 OTH exome AF: 0.00436

GnomAD4 genome AF: 0.00351 AC: 534 AN: 152330 Hom.: 6 Cov.: 33 AF XY: 0.00363 AC XY: 270 AN XY: 74482

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00480

Gnomad4 NFE AF: 0.00462

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00498 Hom.: 3

Bravo AF: 0.00340

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00567

EpiControl AF: 0.00558

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149964084; hg19: chr7-27183146;