rs10835188

Variant names:

• chr11-27501639-G-T
• rs10835188
• NM_018362.4:c.157-73C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

LGR4-AS1 (HGNC:40629): (LGR4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018362.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN7C	NM_018362.4	MANE Select	c.157-73C>A		intron	N/A	NP_060832.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN7C	ENST00000278193.7	TSL:1 MANE Select	c.157-73C>A		intron	N/A	ENSP00000278193.2
	LIN7C	ENST00000524596.1	TSL:1	c.156+163C>A		intron	N/A	ENSP00000435353.1
	LGR4-AS1	ENST00000715842.1		n.432-11362G>T		intron	N/A

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

African (AFR) AF: 0.510 AC: 10723 AN: 21032

American (AMR) AF: 0.543 AC: 14844 AN: 27312

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 16010 AN: 19636

East Asian (EAS) AF: 0.545 AC: 19712 AN: 36200

South Asian (SAS) AF: 0.800 AC: 51657 AN: 64580

European-Finnish (FIN) AF: 0.749 AC: 38083 AN: 50844

Middle Eastern (MID) AF: 0.758 AC: 3448 AN: 4548

European-Non Finnish (NFE) AF: 0.762 AC: 498375 AN: 653824

Other (OTH) AF: 0.737 AC: 30581 AN: 41478

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

African (AFR) AF: 0.525 AC: 21736 AN: 41428

American (AMR) AF: 0.624 AC: 9525 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2831 AN: 3468

East Asian (EAS) AF: 0.579 AC: 2997 AN: 5172

South Asian (SAS) AF: 0.798 AC: 3846 AN: 4818

European-Finnish (FIN) AF: 0.752 AC: 7930 AN: 10540

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52089 AN: 67952

Other (OTH) AF: 0.691 AC: 1455 AN: 2106

Alfa AF: 0.682 Hom.: 22132

Asia WGS AF: 0.685 AC: 2378 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.53
PhyloP100		-0.54
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: rs10835188; hg19: chr11-27523186; COSMIC: COSV53414718;