chr2-37020872-T-C

Variant names:

• chr2-37020872-T-C
• rs17020136
• NM_019024.3:c.3854-36A>G

Variant summary

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

The NM_019024.3(HEATR5B):​c.3854-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,219,088 control chromosomes in the GnomAD database, including 27,457 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 0.19 (3306 hom., cov: 32)
  • Exomes 𝑓: 0.20 (24151 hom.)
• Consequence: HEATR5B NM_019024.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

Genes affected

HEATR5B (HGNC:29273): (HEAT repeat containing 5B) Predicted to be involved in endocytosis; protein localization; and retrograde transport, endosome to Golgi. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR5B	NM_019024.3	c.3854-36A>G		intron_variant	Intron 24 of 35	ENST00000233099.6	NP_061897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR5B	ENST00000233099.6	c.3854-36A>G		intron_variant	Intron 24 of 35	1	NM_019024.3	ENSP00000233099.5

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28286 AN: 151954 Hom.: 3293 Cov.: 32

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.242 AC: 27683 AN: 114490 Hom.: 3610 AF XY: 0.243 AC XY: 15692 AN XY: 64508

Gnomad AFR exome AF: 0.0908

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.525

Gnomad SAS exome AF: 0.319

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.200 AC: 213828 AN: 1067016 Hom.: 24151 Cov.: 14 AF XY: 0.202 AC XY: 106107 AN XY: 525638

Gnomad4 AFR exome AF: 0.0786

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.186 AC: 28323 AN: 152072 Hom.: 3306 Cov.: 32 AF XY: 0.193 AC XY: 14363 AN XY: 74298

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.193

Alfa AF: 0.205 Hom.: 2495

Bravo AF: 0.184

Asia WGS AF: 0.402 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.65

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: rs17020136; hg19: chr2-37248015; COSMIC: COSV51851114;