rs1716543

Positions:

• chr12-80936161-A-C
• chr12-80936161-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004664.4(LIN7A):​c.82+1480T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,040 control chromosomes in the GnomAD database, including 34,081 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 0.64 (34081 hom., cov: 32)
• Consequence: LIN7A NM_004664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIN7A	NM_004664.4	c.82+1480T>G		intron_variant		ENST00000552864.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIN7A	ENST00000552864.6	c.82+1480T>G		intron_variant		1	NM_004664.4	P1
LIN7A	ENST00000549417.5	c.64+1480T>G		intron_variant		1
LIN7A	ENST00000261203.7	c.82+1480T>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96979 AN: 151922 Hom.: 34090 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.638 AC: 97004 AN: 152040 Hom.: 34081 Cov.: 32 AF XY: 0.635 AC XY: 47233 AN XY: 74328

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.689

Alfa AF: 0.776 Hom.: 60775

Bravo AF: 0.622

Asia WGS AF: 0.564 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.79

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: rs1716543; hg19: chr12-81329940;