rs12805648

Variant names:

• chr11-7488335-A-T
• rs12805648
• NM_198474.4:c.338A>T

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198474.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML1	NM_198474.4	MANE Select	c.338A>T	p.Glu113Val	missense	Exon 2 of 3	NP_940876.2
	OLFML1	NM_001370498.1		c.338A>T	p.Glu113Val	missense	Exon 3 of 4	NP_001357427.1
	OLFML1	NM_001370500.1		c.338A>T	p.Glu113Val	missense	Exon 3 of 3	NP_001357429.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML1	ENST00000329293.4	TSL:1 MANE Select	c.338A>T	p.Glu113Val	missense	Exon 2 of 3	ENSP00000332511.3
	OLFML1	ENST00000870572.1		c.338A>T	p.Glu113Val	missense	Exon 2 of 3	ENSP00000540631.1
	OLFML1	ENST00000530135.5	TSL:2	c.338A>T	p.Glu113Val	missense	Exon 3 of 4	ENSP00000433455.1

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

GnomAD2 exomes AF: 0.182 AC: 45695 AN: 251092 AF XY: 0.178

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 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

African (AFR) AF: 0.128 AC: 4284 AN: 33474

American (AMR) AF: 0.260 AC: 11622 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4237 AN: 26134

East Asian (EAS) AF: 0.169 AC: 6708 AN: 39690

South Asian (SAS) AF: 0.143 AC: 12291 AN: 86248

European-Finnish (FIN) AF: 0.209 AC: 11162 AN: 53414

Middle Eastern (MID) AF: 0.107 AC: 617 AN: 5766

European-Non Finnish (NFE) AF: 0.177 AC: 197320 AN: 1111774

Other (OTH) AF: 0.171 AC: 10342 AN: 60388

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

African (AFR) AF: 0.133 AC: 5517 AN: 41520

American (AMR) AF: 0.214 AC: 3272 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3466

East Asian (EAS) AF: 0.174 AC: 900 AN: 5162

South Asian (SAS) AF: 0.148 AC: 715 AN: 4818

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10568

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11532 AN: 67994

Other (OTH) AF: 0.157 AC: 331 AN: 2112

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 v4.9

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
Eigen	Benign	-0.0073
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.9
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.060	B
Vest4		0.28
MPC		0.022
ClinPred		0.024	T
GERP RS		5.7
Varity_R		0.26
gMVP		0.45
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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