rs12986207

Positions:

• chr19-29412770-G-A
• chr19-29412770-G-C

Variant summary

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

The NR_040029.2(VSTM2B-DT):​n.599+5C>T variant causes a splice donor 5th base, intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,358 control chromosomes in the GnomAD database, including 1,991 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 0.15 (1988 hom., cov: 33)
  • Exomes 𝑓: 0.15 (3 hom.)
• Consequence: VSTM2B-DT NR_040029.2 splice_donor_5th_base, intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

VSTM2B-DT (HGNC:27615): (VSTM2B divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSTM2B-DT	NR_040029.2	n.599+5C>T		splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSTM2B-DT	ENST00000582581.5	n.601+5C>T		splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant		2
VSTM2B-DT	ENST00000577849.2	n.604C>T		non_coding_transcript_exon_variant	3/3	3
VSTM2B-DT	ENST00000690107.1	n.401+15961C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22186 AN: 152110 Hom.: 1990 Cov.: 33

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.154 AC: 20 AN: 130 Hom.: 3 Cov.: 0 AF XY: 0.170 AC XY: 16 AN XY: 94

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.146 AC: 22180 AN: 152228 Hom.: 1988 Cov.: 33 AF XY: 0.145 AC XY: 10759 AN XY: 74428

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.192

Alfa AF: 0.160 Hom.: 405

Bravo AF: 0.150

Asia WGS AF: 0.167 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12986207; hg19: chr19-29903677;