15-45402412-C-T

Position:

• chr15-45402412-C-T

Variant summary

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

The NM_024063.3(AFG2B):​c.-18C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,578,396 control chromosomes in the GnomAD database, including 79,495 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 0.32 (8942 hom., cov: 33)
  • Exomes 𝑓: 0.29 (70553 hom.)
• Consequence: AFG2B NM_024063.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

Genes affected

AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]

SPATA5L1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFG2B	NM_024063.3	c.-18C>T		5_prime_UTR_premature_start_codon_gain_variant	1/8	ENST00000305560.11	NP_076968.2
AFG2B	NM_024063.3	c.-18C>T		5_prime_UTR_variant	1/8	ENST00000305560.11	NP_076968.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA5L1	ENST00000305560	c.-18C>T		5_prime_UTR_premature_start_codon_gain_variant	1/8	1	NM_024063.3	ENSP00000305494.6
SPATA5L1	ENST00000305560	c.-18C>T		5_prime_UTR_variant	1/8	1	NM_024063.3	ENSP00000305494.6

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48817 AN: 152036 Hom.: 8921 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.344

GnomAD3 exomes AF: 0.367 AC: 79531 AN: 216806 Hom.: 17906 AF XY: 0.354 AC XY: 42138 AN XY: 118962

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.821

Gnomad SAS exome AF: 0.348

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.293 AC: 418304 AN: 1426242 Hom.: 70553 Cov.: 34 AF XY: 0.294 AC XY: 208307 AN XY: 708984

Gnomad4 AFR exome AF: 0.302

Gnomad4 AMR exome AF: 0.607

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.321 AC: 48865 AN: 152154 Hom.: 8942 Cov.: 33 AF XY: 0.330 AC XY: 24536 AN XY: 74386

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.348

Alfa AF: 0.281 Hom.: 2631

Bravo AF: 0.340

Asia WGS AF: 0.561 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.8
DANN	Benign	0.74

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: rs1365610; hg19: chr15-45694610;