rs35069869

Positions:

• chr3-183245503-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015078.4(MCF2L2):​c.1863-14486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,714 control chromosomes in the GnomAD database, including 8,848 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 0.34 (8848 hom., cov: 31)
• Consequence: MCF2L2 NM_015078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

Genes affected

MCF2L2 (HGNC:30319): (MCF.2 cell line derived transforming sequence-like 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2L2	NM_015078.4	c.1863-14486A>G		intron_variant		ENST00000328913.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2L2	ENST00000328913.8	c.1863-14486A>G		intron_variant		5	NM_015078.4	A2
MCF2L2	ENST00000447025.6	c.1863-14486A>G		intron_variant		1
MCF2L2	ENST00000473233.5	c.1863-14486A>G		intron_variant		5		P4
MCF2L2	ENST00000488149.5	n.2125-14291A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51096 AN: 151596 Hom.: 8837 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.337 AC: 51149 AN: 151714 Hom.: 8848 Cov.: 31 AF XY: 0.340 AC XY: 25218 AN XY: 74124

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.327

Alfa AF: 0.316 Hom.: 947

Bravo AF: 0.334

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.51

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: rs35069869; hg19: chr3-182963291;