17-49040068-T-A

Position:

• chr17-49040068-T-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006546.4(IGF2BP1):​c.795T>A​(p.His265Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00975 in 1,614,098 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (7 hom., cov: 32)
  • Exomes 𝑓: 0.010 (86 hom.)
• Consequence: IGF2BP1 NM_006546.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.738

Genes affected

IGF2BP1 (HGNC:28866): (insulin like growth factor 2 mRNA binding protein 1) This gene encodes a member of the insulin-like growth factor 2 mRNA-binding protein family. The protein encoded by this gene contains four K homology domains and two RNA recognition motifs. It functions by binding to the mRNAs of certain genes, including insulin-like growth factor 2, beta-actin and beta-transducin repeat-containing protein, and regulating their translation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054652393).
• BP6: Variant 17-49040068-T-A is Benign according to our data. Variant chr17-49040068-T-A is described in ClinVar as [Benign]. Clinvar id is 720405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-49040068-T-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP1	NM_006546.4	c.795T>A	p.His265Gln	missense_variant	7/15	ENST00000290341.8	NP_006537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP1	ENST00000290341.8	c.795T>A	p.His265Gln	missense_variant	7/15	1	NM_006546.4	ENSP00000290341.3
IGF2BP1	ENST00000431824.2	c.402-1310T>A		intron_variant		1		ENSP00000389135.2

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 987 AN: 152146 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00886

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00654 AC: 1643 AN: 251286 Hom.: 12 AF XY: 0.00641 AC XY: 871 AN XY: 135824

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.00915

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.0101 AC: 14756 AN: 1461834 Hom.: 86 Cov.: 31 AF XY: 0.00981 AC XY: 7133 AN XY: 727218

Gnomad4 AFR exome AF: 0.00167

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000672

Gnomad4 FIN exome AF: 0.00960

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.00642

GnomAD4 genome AF: 0.00648 AC: 986 AN: 152264 Hom.: 7 Cov.: 32 AF XY: 0.00560 AC XY: 417 AN XY: 74456

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00886

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00778 Hom.: 3

Bravo AF: 0.00594

TwinsUK AF: 0.0127 AC: 47

ALSPAC AF: 0.0138 AC: 53

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0107 AC: 92

ExAC AF: 0.00679 AC: 824

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00943

EpiControl AF: 0.00848

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	IGF2BP1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.9
DANN	Benign	0.82
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.0	N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.051
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.29		Gain of loop (P = 0.0851);
MVP		0.27
MPC		0.91
ClinPred		0.00084	T
GERP RS		-2.9
Varity_R		0.11
gMVP		0.77

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: rs61751193; hg19: chr17-47117430; COSMIC: COSV51736597; COSMIC: COSV51736597;