rs12805648

chr11-7488335-A-T

Variant summary

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

The NM_198474.4(OLFML1):c.338A>T(p.Glu113Val) variant causes a missense change. The variant allele was found at a frequency of 0.176 in 1,613,724 control chromosomes in the GnomAD database, including 25,534 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2219 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23315 hom.)
• Consequence: OLFML1 NM_198474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95

Genes affected

OLFML1 (HGNC:24473): (olfactomedin like 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SYT9-AS1 (HGNC:56173): (SYT9 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016070008).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLFML1	NM_198474.4	c.338A>T	p.Glu113Val	missense_variant	2/3	ENST00000329293.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML1	ENST00000329293.4	c.338A>T	p.Glu113Val	missense_variant	2/3	1	NM_198474.4	P1
SYT9-AS1	ENST00000530201.2	n.1350+23788T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25279 AN: 152000 Hom.: 2217 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.182 AC: 45695 AN: 251092 Hom.: 4496 AF XY: 0.178 AC XY: 24170 AN XY: 135692

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.267

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.177 AC: 258583 AN: 1461606 Hom.: 23315 Cov.: 33 AF XY: 0.175 AC XY: 127550 AN XY: 727128

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.166 AC: 25307 AN: 152118 Hom.: 2219 Cov.: 32 AF XY: 0.170 AC XY: 12644 AN XY: 74356

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.157

Alfa AF: 0.168 Hom.: 1688

Bravo AF: 0.165

TwinsUK AF: 0.176 AC: 652

ALSPAC AF: 0.176 AC: 679

ESP6500AA AF: 0.132 AC: 579

ESP6500EA AF: 0.169 AC: 1455

ExAC AF: 0.177 AC: 21513

Asia WGS AF: 0.165 AC: 575 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.0073
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.89	D
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.66	P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.060	B;B
Vest4		0.28
MPC		0.022
ClinPred		0.024	T
GERP RS		5.7
Varity_R		0.26
gMVP		0.45

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: rs12805648; hg19: chr11-7509566; COSMIC: COSV61402237; COSMIC: COSV61402237;