chr19-35739579-G-C

Variant names:

• chr19-35739579-G-C
• rs143428422
• NM_024660.4:c.769C>G

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.769C>G​(p.Leu257Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L257M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IGFLR1 NM_024660.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 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=0.22072202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFLR1	NM_024660.4	c.769C>G	p.Leu257Val	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.769C>G	p.Leu257Val	missense_variant	Exon 5 of 5	1	NM_024660.4	ENSP00000246532.1
ENSG00000267120	ENST00000589807.1	n.*1263C>G		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000472696.1
ENSG00000267120	ENST00000589807.1	n.*1263C>G		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000472696.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T;.;.;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	.;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.3	M;.;.;M
PhyloP100		2.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.0	D;.;.;.
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.21
MutPred		0.21		Loss of helix (P = 0.0558);.;.;Loss of helix (P = 0.0558);
MVP		0.69
MPC		0.47
ClinPred		0.99	D
GERP RS		1.2
Varity_R		0.62
gMVP		0.48
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143428422; hg19: chr19-36230480;