19-9856753-C-T

Position:

• chr19-9856753-C-T

Variant summary

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

The NM_058164.4(OLFM2):​c.687+54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,461,562 control chromosomes in the GnomAD database, including 2,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (165 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2534 hom.)
• Consequence: OLFM2 NM_058164.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-9856753-C-T is Benign according to our data. Variant chr19-9856753-C-T is described in ClinVar as [Benign]. Clinvar id is 1286451.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLFM2	NM_058164.4	c.687+54G>A		intron_variant		ENST00000264833.9
OLFM2	NM_001304347.2	c.759+54G>A		intron_variant
OLFM2	NM_001304348.2	c.453+54G>A		intron_variant
OLFM2	XM_047439713.1	c.483+54G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFM2	ENST00000264833.9	c.687+54G>A		intron_variant		1	NM_058164.4
OLFM2	ENST00000590841.5	c.453+54G>A		intron_variant		2
OLFM2	ENST00000593091.2	c.759+54G>A		intron_variant		5		P1
OLFM2	ENST00000592448.1	c.*92+54G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5999 AN: 152134 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.0278

GnomAD4 exome AF: 0.0578 AC: 75682 AN: 1309310 Hom.: 2534 AF XY: 0.0571 AC XY: 37256 AN XY: 652528

Gnomad4 AFR exome AF: 0.00965

Gnomad4 AMR exome AF: 0.0518

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.000133

Gnomad4 SAS exome AF: 0.0388

Gnomad4 FIN exome AF: 0.0585

Gnomad4 NFE exome AF: 0.0649

Gnomad4 OTH exome AF: 0.0476

GnomAD4 genome AF: 0.0394 AC: 5996 AN: 152252 Hom.: 165 Cov.: 32 AF XY: 0.0390 AC XY: 2907 AN XY: 74444

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.0488

Gnomad4 NFE AF: 0.0585

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0512 Hom.: 26

Bravo AF: 0.0380

Asia WGS AF: 0.0130 AC: 46 AN: 3478

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

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.76

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: rs34631855; hg19: chr19-9967429;