11-27501639-G-T

Position:

• chr11-27501639-G-T

Variant summary

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

The NM_018362.4(LIN7C):​c.157-73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,071,410 control chromosomes in the GnomAD database, including 292,908 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 (36210 hom., cov: 32)
  • Exomes 𝑓: 0.74 (256698 hom.)
• Consequence: LIN7C NM_018362.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541

Genes affected

LIN7C (HGNC:17789): (lin-7 homolog C, crumbs cell polarity complex component) Enables L27 domain binding activity and cytoskeletal protein binding activity. Involved in morphogenesis of an epithelial sheet. Located in cell-cell junction; cytoplasm; and plasma membrane. Part of MPP7-DLG1-LIN7 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIN7C	NM_018362.4	c.157-73C>A		intron_variant		ENST00000278193.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIN7C	ENST00000278193.7	c.157-73C>A		intron_variant		1	NM_018362.4	P1
LIN7C	ENST00000524596.1	c.156+163C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103374 AN: 151838 Hom.: 36211 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.743 AC: 683433 AN: 919454 Hom.: 256698 Cov.: 12 AF XY: 0.748 AC XY: 352609 AN XY: 471306

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.815

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.737

GnomAD4 genome AF: 0.680 AC: 103385 AN: 151956 Hom.: 36210 Cov.: 32 AF XY: 0.683 AC XY: 50697 AN XY: 74266

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.691

Alfa AF: 0.676 Hom.: 10220

Asia WGS AF: 0.685 AC: 2378 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.53

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: rs10835188; hg19: chr11-27523186; COSMIC: COSV53414718;