11-7488293-T-C

Variant names:

• chr11-7488293-T-C
• rs375267113
• NM_198474.4:c.296T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198474.4(OLFML1):​c.296T>C​(p.Ile99Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000225 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: OLFML1 NM_198474.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1313121).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML1	NM_198474.4	MANE Select	c.296T>C	p.Ile99Thr	missense	Exon 2 of 3	NP_940876.2	Q6UWY5
	OLFML1	NM_001370498.1		c.296T>C	p.Ile99Thr	missense	Exon 3 of 4	NP_001357427.1	Q6UWY5
	OLFML1	NM_001370500.1		c.296T>C	p.Ile99Thr	missense	Exon 3 of 3	NP_001357429.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML1	ENST00000329293.4	TSL:1 MANE Select	c.296T>C	p.Ile99Thr	missense	Exon 2 of 3	ENSP00000332511.3	Q6UWY5
	OLFML1	ENST00000870572.1		c.296T>C	p.Ile99Thr	missense	Exon 2 of 3	ENSP00000540631.1
	OLFML1	ENST00000530135.5	TSL:2	c.296T>C	p.Ile99Thr	missense	Exon 3 of 4	ENSP00000433455.1	Q6UWY5

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 67 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000175 AC: 44 AN: 251310 AF XY: 0.000199

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000202 AC: 296 AN: 1461846 Hom.: 0 Cov.: 31 AF XY: 0.000194 AC XY: 141 AN XY: 727226

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.000425 AC: 19 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000224 AC: 249 AN: 1111982

Other (OTH) AF: 0.000149 AC: 9 AN: 60392

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.000578 AC XY: 43 AN XY: 74442

African (AFR) AF: 0.000241 AC: 10 AN: 41548

American (AMR) AF: 0.00281 AC: 43 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.000412

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.88	P
Vest4		0.59
MVP		0.74
MPC		0.056
ClinPred		0.16	T
GERP RS		5.8
Varity_R		0.22
gMVP		0.34
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs375267113; hg19: chr11-7509524;