rs1163662

Positions:

• chr12-80898148-G-A

Variant summary

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

The NM_004664.4(LIN7A):​c.83-8779C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,156 control chromosomes in the GnomAD database, including 39,150 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 0.68 (39150 hom., cov: 33)
• Consequence: LIN7A NM_004664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN7A	NM_004664.4	c.83-8779C>T		intron_variant		ENST00000552864.6	NP_004655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN7A	ENST00000552864.6	c.83-8779C>T		intron_variant		1	NM_004664.4	ENSP00000447488	P1
LIN7A	ENST00000549417.5	c.65-8779C>T		intron_variant		1		ENSP00000448975
LIN7A	ENST00000261203.7	c.83-8779C>T		intron_variant, NMD_transcript_variant		1		ENSP00000261203

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103395 AN: 152036 Hom.: 39144 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.680 AC: 103418 AN: 152156 Hom.: 39150 Cov.: 33 AF XY: 0.679 AC XY: 50539 AN XY: 74402

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.719

Alfa AF: 0.763 Hom.: 5910

Bravo AF: 0.643

Asia WGS AF: 0.587 AC: 2043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.80
DANN	Benign	0.45

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: rs1163662; hg19: chr12-81291927;