rs2682818

Positions:

• chr12-80935757-A-C
• chr12-80935757-A-T

Variant summary

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

The NM_004664.4(LIN7A):​c.82+1884T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 500,570 control chromosomes in the GnomAD database, including 171,423 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 0.81 (50012 hom., cov: 31)
  • Exomes 𝑓: 0.83 (121411 hom.)
• Consequence: LIN7A NM_004664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

Genes affected

LIN7A (HGNC:17787): (lin-7 homolog A, crumbs cell polarity complex component) The protein encoded by this gene is involved in generating and maintaining the asymmetric distribution of channels and receptors at the cell membrane. The encoded protein also is required for the localization of some specific channels and can be part of a protein complex that couples synaptic vesicle exocytosis to cell adhesion in the brain. [provided by RefSeq, May 2016]

MIR618 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN7A	NM_004664.4	c.82+1884T>G		intron_variant		ENST00000552864.6	NP_004655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN7A	ENST00000552864.6	c.82+1884T>G		intron_variant		1	NM_004664.4	ENSP00000447488.1
LIN7A	ENST00000549417.5	c.64+1884T>G		intron_variant		1		ENSP00000448975.1
LIN7A	ENST00000261203.7	n.82+1884T>G		intron_variant		1		ENSP00000261203.3
MIR618	ENST00000385287.1	n.77T>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122677 AN: 151890 Hom.: 49990 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.843

GnomAD3 exomes AF: 0.833 AC: 208552 AN: 250244 Hom.: 87661 AF XY: 0.829 AC XY: 112371 AN XY: 135484

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.927

Gnomad ASJ exome AF: 0.894

Gnomad EAS exome AF: 0.746

Gnomad SAS exome AF: 0.733

Gnomad FIN exome AF: 0.834

Gnomad NFE exome AF: 0.860

Gnomad OTH exome AF: 0.854

GnomAD4 exome AF: 0.831 AC: 289711 AN: 348562 Hom.: 121411 Cov.: 0 AF XY: 0.822 AC XY: 161976 AN XY: 197136

Gnomad4 AFR exome AF: 0.691

Gnomad4 AMR exome AF: 0.926

Gnomad4 ASJ exome AF: 0.896

Gnomad4 EAS exome AF: 0.748

Gnomad4 SAS exome AF: 0.734

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.840

GnomAD4 genome AF: 0.808 AC: 122753 AN: 152008 Hom.: 50012 Cov.: 31 AF XY: 0.806 AC XY: 59902 AN XY: 74292

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.843

Alfa AF: 0.836 Hom.: 26637

Bravo AF: 0.809

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.0
DANN	Benign	0.58

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: rs2682818; hg19: chr12-81329536; COSMIC: COSV54019323; COSMIC: COSV54019323;