12-80845942-GA-G

Position:

• chr12-80845942-GA-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_004664.4(LIN7A):​c.274-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (1 hom., cov: 32)
  • Exomes 𝑓: 0.22 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIN7A NM_004664.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.948

Genes affected

LIN7A (HGNC:17787): (lin-7 homolog A, crumbs cell polarity complex component) The protein encoded by this gene is involved in generating and maintaining the asymmetric distribution of channels and receptors at the cell membrane. The encoded protein also is required for the localization of some specific channels and can be part of a protein complex that couples synaptic vesicle exocytosis to cell adhesion in the brain. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 12-80845942-GA-G is Benign according to our data. Variant chr12-80845942-GA-G is described in ClinVar as [Benign]. Clinvar id is 218645.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIN7A	NM_004664.4	c.274-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000552864.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIN7A	ENST00000552864.6	c.274-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004664.4	P1
LIN7A	ENST00000549417.5	c.256-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
LIN7A	ENST00000261203.7	c.*45-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1
LIN7A	ENST00000552093.1	c.171-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 646 AN: 127116 Hom.: 1 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00568

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00475

Gnomad ASJ AF: 0.00261

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.0125

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.00370

Gnomad NFE AF: 0.00372

Gnomad OTH AF: 0.00696

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.219 AC: 225235 AN: 1030536 Hom.: 0 Cov.: 0 AF XY: 0.221 AC XY: 112969 AN XY: 512184

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00513 AC: 652 AN: 127136 Hom.: 1 Cov.: 32 AF XY: 0.00573 AC XY: 349 AN XY: 60926

Gnomad4 AFR AF: 0.00576

Gnomad4 AMR AF: 0.00483

Gnomad4 ASJ AF: 0.00261

Gnomad4 EAS AF: 0.00311

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.00372

Gnomad4 OTH AF: 0.00748

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jul 15, 2015

- -

Computational scores

Source: dbNSFP v4.3

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: rs79919291; hg19: chr12-81239721;