chr14-74105395-C-A

Variant names:

• chr14-74105395-C-A
• rs1468507
• NM_001024674.3:c.283+4157C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001024674.3(LIN52):​c.283+4157C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,908 control chromosomes in the GnomAD database, including 20,018 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 0.51 (20018 hom., cov: 31)
• Consequence: LIN52 NM_001024674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 6 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]

LOC105370563 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN52	NM_001024674.3	c.283+4157C>A		intron_variant	Intron 5 of 5	ENST00000555028.7	NP_001019845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN52	ENST00000555028.7	c.283+4157C>A		intron_variant	Intron 5 of 5	1	NM_001024674.3	ENSP00000451812.2
LIN52	ENST00000554938.2	c.217+7535C>A		intron_variant	Intron 4 of 4	4		ENSP00000452513.2
LIN52	ENST00000553404.5	n.822+7535C>A		intron_variant	Intron 4 of 4	2
LIN52	ENST00000554076.5	n.295+4157C>A		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76665 AN: 151788 Hom.: 19985 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.505 AC: 76744 AN: 151908 Hom.: 20018 Cov.: 31 AF XY: 0.507 AC XY: 37601 AN XY: 74232

African (AFR) AF: 0.508 AC: 21061 AN: 41434

American (AMR) AF: 0.503 AC: 7671 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4620 AN: 5178

South Asian (SAS) AF: 0.706 AC: 3403 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4528 AN: 10512

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.472 AC: 32075 AN: 67932

Other (OTH) AF: 0.515 AC: 1083 AN: 2104

Alfa AF: 0.486 Hom.: 24224

Bravo AF: 0.515

Asia WGS AF: 0.712 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.28
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1468507; hg19: chr14-74572098;