15-100569122-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAA

Variant names:

• chr15-100569122-C-CAAAA
• rs56225071
• NM_001040616.3:c.*112_*115dupTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001040616.3(LINS1):​c.*112_*115dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0072 (2 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

Genes affected

LINS1 (HGNC:30922): (lines homolog 1) The Drosophila segment polarity gene lin encodes a protein, lines, which plays important roles in development of the epidermis and hindgut. This gene encodes a protein containing a lines-like domain. This gene is located on chromosome 15 and clustered with the gene encoding ankyrin repeat and SOCS box-containing protein 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00723 (2665/368472) while in subpopulation NFE AF= 0.00806 (1840/228216). AF 95% confidence interval is 0.00776. There are 2 homozygotes in gnomad4_exome. There are 1380 alleles in male gnomad4_exome subpopulation. Median coverage is 5. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*112_*115dupTTTT		3_prime_UTR_variant	Exon 7 of 7	ENST00000314742.13	NP_001035706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINS1	ENST00000314742	c.*112_*115dupTTTT		3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000560783.1	n.191-3861_191-3858dupTTTT		intron_variant	Intron 1 of 3	5		ENSP00000474128.1
LINS1	ENST00000559169.1	n.*109_*112dupTTTT		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000236 AC: 25 AN: 106068 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000108

Gnomad ASJ AF: 0.000347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000336

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000273

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00723 AC: 2665 AN: 368472 Hom.: 2 Cov.: 5 AF XY: 0.00710 AC XY: 1380 AN XY: 194494

Gnomad4 AFR exome AF: 0.00750

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.00881

Gnomad4 EAS exome AF: 0.00162

Gnomad4 SAS exome AF: 0.00751

Gnomad4 FIN exome AF: 0.00590

Gnomad4 NFE exome AF: 0.00806

Gnomad4 OTH exome AF: 0.00710

GnomAD4 genome AF: 0.000236 AC: 25 AN: 106054 Hom.: 0 Cov.: 0 AF XY: 0.000267 AC XY: 13 AN XY: 48606

Gnomad4 AFR AF: 0.000254

Gnomad4 AMR AF: 0.000108

Gnomad4 ASJ AF: 0.000347

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000339

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000273

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56225071; hg19: chr15-101109327;