19-49115283-G-A

Variant names:

• chr19-49115283-G-A
• rs375527609
• NM_022165.3:c.180G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_022165.3(LIN7B):​c.180G>A​(p.Thr60Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T60T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIN7B NM_022165.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 0 publications found

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]

ENSG00000297778 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022165.3. 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
	LIN7B	NM_022165.3	MANE Select	c.180G>A	p.Thr60Thr	synonymous	Exon 3 of 6	NP_071448.1	Q9HAP6-1
	LIN7B	NM_001308419.2		c.180G>A	p.Thr60Thr	synonymous	Exon 3 of 5	NP_001295348.1	Q9HAP6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN7B	ENST00000221459.7	TSL:1 MANE Select	c.180G>A	p.Thr60Thr	synonymous	Exon 3 of 6	ENSP00000221459.2	Q9HAP6-1
	LIN7B	ENST00000391864.7	TSL:3	c.180G>A	p.Thr60Thr	synonymous	Exon 3 of 5	ENSP00000375737.3	Q9HAP6-2
	LIN7B	ENST00000486217.2	TSL:2	c.159G>A	p.Thr53Thr	synonymous	Exon 3 of 3	ENSP00000474643.1	S4R3R4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 173800 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1411228 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 697234

African (AFR) AF: 0.00 AC: 0 AN: 32260

American (AMR) AF: 0.00 AC: 0 AN: 37548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25238

East Asian (EAS) AF: 0.00 AC: 0 AN: 36962

South Asian (SAS) AF: 0.00 AC: 0 AN: 80122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085138

Other (OTH) AF: 0.00 AC: 0 AN: 58434

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		-1.9

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: rs375527609; hg19: chr19-49618540;