chr7-27130540-C-T

Position:

• chr7-27130540-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002141.5(HOXA4):​c.194G>A​(p.Gly65Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 1,370,354 control chromosomes in the GnomAD database, including 7,914 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1594 hom., cov: 31)
  • Exomes 𝑓: 0.094 (6320 hom.)
• Consequence: HOXA4 NM_002141.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.582

Genes affected

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]

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]

ENSG00000273433 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024381578).
• BP6: Variant 7-27130540-C-T is Benign according to our data. Variant chr7-27130540-C-T is described in ClinVar as [Benign]. Clinvar id is 1237183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA4	NM_002141.5	c.194G>A	p.Gly65Asp	missense_variant	1/2	ENST00000360046.10	NP_002132.3
HOXA3	NM_153631.3	c.-389-3470G>A		intron_variant		ENST00000612286.5	NP_705895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA4	ENST00000360046.10	c.194G>A	p.Gly65Asp	missense_variant	1/2	1	NM_002141.5	ENSP00000353151.5
HOXA3	ENST00000612286.5	c.-389-3470G>A		intron_variant		2	NM_153631.3	ENSP00000484411.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20034 AN: 150430 Hom.: 1591 Cov.: 31

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0630

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0672

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0929

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.119 AC: 6144 AN: 51644 Hom.: 574 AF XY: 0.109 AC XY: 3220 AN XY: 29658

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.0499

Gnomad EAS exome AF: 0.159

Gnomad SAS exome AF: 0.0616

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.0928

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.0945 AC: 115215 AN: 1219820 Hom.: 6320 Cov.: 34 AF XY: 0.0937 AC XY: 55781 AN XY: 595170

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.0586

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.0656

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0884

Gnomad4 OTH exome AF: 0.0974

GnomAD4 genome AF: 0.133 AC: 20053 AN: 150534 Hom.: 1594 Cov.: 31 AF XY: 0.134 AC XY: 9843 AN XY: 73500

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0630

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.0668

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0890

Gnomad4 OTH AF: 0.114

Alfa AF: 0.115 Hom.: 147

Bravo AF: 0.144

TwinsUK AF: 0.0858 AC: 318

ALSPAC AF: 0.0859 AC: 331

ESP6500AA AF: 0.155 AC: 255

ESP6500EA AF: 0.0688 AC: 269

ExAC AF: 0.0766 AC: 4419

Asia WGS AF: 0.0920 AC: 310 AN: 3348

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

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.48	.;.;T
MetaRNN	Benign	0.0024	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.29	.;N;N
REVEL	Benign	0.047
Sift	Benign	0.17	.;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.099	B;B;B
Vest4		0.082
MPC		1.6
ClinPred		0.011	T
GERP RS		2.0
Varity_R		0.094
gMVP		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

Publications

LitVar

Other links and lift over

dbSNP: rs6962314; hg19: chr7-27170159; COSMIC: COSV57825566; COSMIC: COSV57825566;