19-49116304-T-C

Variant names:

• chr19-49116304-T-C
• rs28446007
• NM_022165.3:c.270T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_022165.3(LIN7B):​c.270T>C​(p.His90His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,614,024 control chromosomes in the GnomAD database, including 105 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 0.014 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (66 hom.)
• Consequence: LIN7B NM_022165.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 2 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.014 (2132/152228) while in subpopulation AFR AF = 0.0392 (1630/41538). AF 95% confidence interval is 0.0377. There are 39 homozygotes in GnomAd4. There are 960 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2132 AD gene.

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.270T>C	p.His90His	synonymous	Exon 4 of 6	NP_071448.1	Q9HAP6-1
	LIN7B	NM_001308419.2		c.228+973T>C		intron	N/A	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.270T>C	p.His90His	synonymous	Exon 4 of 6	ENSP00000221459.2	Q9HAP6-1
	LIN7B	ENST00000882750.1		c.198T>C	p.His66His	synonymous	Exon 3 of 5	ENSP00000552809.1
	LIN7B	ENST00000391864.7	TSL:3	c.228+973T>C		intron	N/A	ENSP00000375737.3	Q9HAP6-2

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2129 AN: 152110 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00732 AC: 1836 AN: 250776 AF XY: 0.00653

Gnomad AFR exome AF: 0.0413

Gnomad AMR exome AF: 0.00802

Gnomad ASJ exome AF: 0.0443

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00319

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00375 AC: 5477 AN: 1461796 Hom.: 66 Cov.: 31 AF XY: 0.00367 AC XY: 2666 AN XY: 727188

African (AFR) AF: 0.0384 AC: 1284 AN: 33478

American (AMR) AF: 0.00801 AC: 358 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0430 AC: 1124 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000533 AC: 46 AN: 86252

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53414

Middle Eastern (MID) AF: 0.0223 AC: 128 AN: 5746

European-Non Finnish (NFE) AF: 0.00178 AC: 1974 AN: 1111964

Other (OTH) AF: 0.00929 AC: 561 AN: 60386

GnomAD4 genome AF: 0.0140 AC: 2132 AN: 152228 Hom.: 39 Cov.: 32 AF XY: 0.0129 AC XY: 960 AN XY: 74418

African (AFR) AF: 0.0392 AC: 1630 AN: 41538

American (AMR) AF: 0.00771 AC: 118 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00257 AC: 175 AN: 68004

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.0104 Hom.: 14

Bravo AF: 0.0161

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.6
DANN	Benign	0.75
PhyloP100		0.21
Mutation Taster		=83/17	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: rs28446007; hg19: chr19-49619561;