14-74085267-G-C

Position:

• chr14-74085267-G-C

Variant summary

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

The NM_001024674.3(LIN52):​c.19+274G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 351,776 control chromosomes in the GnomAD database, including 30,338 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 0.40 (13025 hom., cov: 31)
  • Exomes 𝑓: 0.39 (17313 hom.)
• Consequence: LIN52 NM_001024674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

LIN52 (HGNC:19856): (lin-52 DREAM MuvB core complex component) Predicted to be involved in transcription, DNA-templated. Predicted to be located in nucleoplasm. Predicted to be part of DRM complex. [provided by Alliance of Genome Resources, Apr 2022]

LIN52 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN52	NM_001024674.3	c.19+274G>C		intron_variant		ENST00000555028.7	NP_001019845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN52	ENST00000555028.7	c.19+274G>C		intron_variant		1	NM_001024674.3	ENSP00000451812.2
LIN52	ENST00000554938.2	c.19+274G>C		intron_variant		4		ENSP00000452513.2
LIN52	ENST00000553404.5	n.308G>C		non_coding_transcript_exon_variant	1/5	2
LIN52	ENST00000554076.5	n.31+274G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60179 AN: 151698 Hom.: 12995 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.386 AC: 77203 AN: 199960 Hom.: 17313 Cov.: 2 AF XY: 0.383 AC XY: 38583 AN XY: 100670

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.826

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.397 AC: 60255 AN: 151816 Hom.: 13025 Cov.: 31 AF XY: 0.398 AC XY: 29494 AN XY: 74186

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.405

Alfa AF: 0.335 Hom.: 5186

Bravo AF: 0.403

Asia WGS AF: 0.641 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs2239557; hg19: chr14-74551970;