10-92692673-T-G

Position:

• chr10-92692673-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002729.5(HHEX):​c.541-29T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,612,120 control chromosomes in the GnomAD database, including 10,023 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1050 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8973 hom.)
• Consequence: HHEX NM_002729.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

Genes affected

HHEX (HGNC:4901): (hematopoietically expressed homeobox) This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHEX	NM_002729.5	c.541-29T>G		intron_variant		ENST00000282728.10	NP_002720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHEX	ENST00000282728.10	c.541-29T>G		intron_variant		1	NM_002729.5	ENSP00000282728	P1
HHEX	ENST00000492654.3	c.25-29T>G		intron_variant		1		ENSP00000447953
HHEX	ENST00000472590.6	c.25-29T>G		intron_variant		2		ENSP00000450017

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17090 AN: 151558 Hom.: 1050 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.0978 AC: 24503 AN: 250624 Hom.: 1381 AF XY: 0.0948 AC XY: 12854 AN XY: 135572

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.0514

Gnomad SAS exome AF: 0.0543

Gnomad FIN exome AF: 0.0581

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.106 AC: 155297 AN: 1460444 Hom.: 8973 Cov.: 31 AF XY: 0.105 AC XY: 76315 AN XY: 726582

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.0423

Gnomad4 SAS exome AF: 0.0539

Gnomad4 FIN exome AF: 0.0591

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.113 AC: 17109 AN: 151676 Hom.: 1050 Cov.: 32 AF XY: 0.109 AC XY: 8051 AN XY: 74088

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.0420

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.112

Alfa AF: 0.114 Hom.: 1269

Bravo AF: 0.119

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.0
DANN	Benign	0.54

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: rs2275729; hg19: chr10-94452430;