rs3751547

Variant names:

• chr15-100568921-T-C
• rs3751547
• NM_001040616.3:c.*317A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040616.3(LINS1):​c.*317A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 228,660 control chromosomes in the GnomAD database, including 37,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24201 hom., cov: 29)
  • Exomes 𝑓: 0.59 (13774 hom.)
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.23
• Publications: 0 publications found

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]

LINS1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal recessive 27

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 15-100568921-T-C is Benign according to our data. Variant chr15-100568921-T-C is described in ClinVar as [Benign]. Clinvar id is 1220592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.*317A>G		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	ENST00000314742.13	c.*317A>G		3_prime_UTR_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000560783.1	n.191-3656A>G		intron_variant	Intron 1 of 3	5		ENSP00000474128.1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84447 AN: 151578 Hom.: 24187 Cov.: 29

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.585 AC: 45062 AN: 76966 Hom.: 13774 Cov.: 0 AF XY: 0.582 AC XY: 24568 AN XY: 42214

African (AFR) AF: 0.408 AC: 577 AN: 1414

American (AMR) AF: 0.596 AC: 2337 AN: 3918

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 769 AN: 1724

East Asian (EAS) AF: 0.267 AC: 1083 AN: 4062

South Asian (SAS) AF: 0.566 AC: 7045 AN: 12450

European-Finnish (FIN) AF: 0.588 AC: 1557 AN: 2646

Middle Eastern (MID) AF: 0.519 AC: 111 AN: 214

European-Non Finnish (NFE) AF: 0.630 AC: 29594 AN: 46982

Other (OTH) AF: 0.559 AC: 1989 AN: 3556

GnomAD4 genome AF: 0.557 AC: 84510 AN: 151694 Hom.: 24201 Cov.: 29 AF XY: 0.557 AC XY: 41277 AN XY: 74092

African (AFR) AF: 0.433 AC: 17927 AN: 41362

American (AMR) AF: 0.561 AC: 8547 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1736 AN: 3466

East Asian (EAS) AF: 0.321 AC: 1646 AN: 5132

South Asian (SAS) AF: 0.576 AC: 2767 AN: 4802

European-Finnish (FIN) AF: 0.629 AC: 6593 AN: 10488

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43451 AN: 67910

Other (OTH) AF: 0.568 AC: 1197 AN: 2106

Alfa AF: 0.599 Hom.: 3483

Bravo AF: 0.543

Asia WGS AF: 0.490 AC: 1707 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.35
PhyloP100		-2.2
Mutation Taster		=100/0	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: rs3751547; hg19: chr15-101109126;