19-49114449-T-C

Variant names:

• chr19-49114449-T-C
• rs10419132
• NM_022165.3:c.37+8T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022165.3(LIN7B):​c.37+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,206,518 control chromosomes in the GnomAD database, including 85,062 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11626 hom., cov: 34)
  • Exomes 𝑓: 0.37 (73436 hom.)
• Consequence: LIN7B NM_022165.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001044
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.05

Genes affected

LIN7B (HGNC:17788): (lin-7 homolog B, crumbs cell polarity complex component) Enables protein domain specific binding activity. Predicted to be involved in maintenance of epithelial cell apical/basal polarity; neurotransmitter secretion; and protein localization to basolateral plasma membrane. Predicted to be located in plasma membrane. Predicted to be part of MPP7-DLG1-LIN7 complex. Predicted to be active in basolateral plasma membrane; cell-cell junction; and synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 19-49114449-T-C is Benign according to our data. Variant chr19-49114449-T-C is described in ClinVar as [Benign]. Clinvar id is 1279757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN7B	NM_022165.3	c.37+8T>C		splice_region_variant, intron_variant	Intron 1 of 5	ENST00000221459.7	NP_071448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN7B	ENST00000221459.7	c.37+8T>C		splice_region_variant, intron_variant	Intron 1 of 5	1	NM_022165.3	ENSP00000221459.2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58413 AN: 151460 Hom.: 11606 Cov.: 34

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.371 AC: 391866 AN: 1054952 Hom.: 73436 Cov.: 31 AF XY: 0.372 AC XY: 185448 AN XY: 497900

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.386 AC: 58473 AN: 151566 Hom.: 11626 Cov.: 34 AF XY: 0.380 AC XY: 28135 AN XY: 74064

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.394

Alfa AF: 0.373 Hom.: 1316

Bravo AF: 0.399

Asia WGS AF: 0.336 AC: 1099 AN: 3270

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 05, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

LIN7B-related disorder Benign:1

Nov 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.0
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: rs10419132; hg19: chr19-49617706;