chr14-74085267-G-C

Variant names:

• chr14-74085267-G-C
• rs2239557
• NM_001024674.3:c.19+274G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LIN52	NM_001024674.3	c.19+274G>C		intron_variant	Intron 1 of 5	ENST00000555028.7	NP_001019845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN52	ENST00000555028.7	c.19+274G>C		intron_variant	Intron 1 of 5	1	NM_001024674.3	ENSP00000451812.2

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

African (AFR) AF: 0.499 AC: 3105 AN: 6220

American (AMR) AF: 0.311 AC: 1794 AN: 5760

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 2789 AN: 8026

East Asian (EAS) AF: 0.826 AC: 15730 AN: 19040

South Asian (SAS) AF: 0.632 AC: 1198 AN: 1896

European-Finnish (FIN) AF: 0.285 AC: 4414 AN: 15488

Middle Eastern (MID) AF: 0.476 AC: 521 AN: 1094

European-Non Finnish (NFE) AF: 0.330 AC: 42542 AN: 128912

Other (OTH) AF: 0.378 AC: 5110 AN: 13524

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

African (AFR) AF: 0.493 AC: 20396 AN: 41378

American (AMR) AF: 0.314 AC: 4799 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1160 AN: 3470

East Asian (EAS) AF: 0.816 AC: 4194 AN: 5140

South Asian (SAS) AF: 0.599 AC: 2877 AN: 4806

European-Finnish (FIN) AF: 0.283 AC: 2993 AN: 10560

Middle Eastern (MID) AF: 0.490 AC: 142 AN: 290

European-Non Finnish (NFE) AF: 0.330 AC: 22383 AN: 67910

Other (OTH) AF: 0.405 AC: 850 AN: 2098

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
PhyloP100		-1.2
PromoterAI		-0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2239557; hg19: chr14-74551970;