chr19-35739500-C-G

Variant names:

• chr19-35739500-C-G
• rs200099438
• NM_024660.4:c.848G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024660.4(IGFLR1):​c.848G>C​(p.Arg283Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R283Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IGFLR1 NM_024660.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 3 publications found

Genes affected

IGFLR1 (HGNC:23620): (IGF like family receptor 1) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267120 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24897695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFLR1	NM_024660.4	c.848G>C	p.Arg283Pro	missense_variant	Exon 5 of 5	ENST00000246532.6	NP_078936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFLR1	ENST00000246532.6	c.848G>C	p.Arg283Pro	missense_variant	Exon 5 of 5	1	NM_024660.4	ENSP00000246532.1
ENSG00000267120	ENST00000589807.1	n.*1342G>C		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000472696.1
ENSG00000267120	ENST00000589807.1	n.*1342G>C		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000472696.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461680 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727124

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.66	.;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;.;M
PhyloP100		1.4
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.4	D;.;.;.
REVEL	Benign	0.17
Sift	Uncertain	0.011	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.40	B;B;.;B
Vest4		0.55
MutPred		0.47		Loss of MoRF binding (P = 0.0239);.;.;Loss of MoRF binding (P = 0.0239);
MVP		0.28
MPC		0.56
ClinPred		0.97	D
GERP RS		2.9
Varity_R		0.81
gMVP		0.80
Mutation Taster		=71/29	polymorphism

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: rs200099438; hg19: chr19-36230401;