NM_001040616.3:c.*167A>G

Variant names:

• chr15-100569071-T-C
• rs3751552
• NM_001040616.3:c.*167A>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.*167A>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 0.384 in 143,386 control chromosomes in the GnomAD database, including 11,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11115 hom., cov: 23)
  • Exomes 𝑓: 0.39 (28946 hom.)
  • Failed GnomAD Quality Control
• Consequence: LINS1 NM_001040616.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-1.02).
• BP6: Variant 15-100569071-T-C is Benign according to our data. Variant chr15-100569071-T-C is described in ClinVar as Benign. ClinVar VariationId is 1281579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040616.3. 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
	LINS1	NM_001040616.3	MANE Select	c.*167A>G		3_prime_UTR	Exon 7 of 7	NP_001035706.2	Q8NG48-1
	LINS1	NM_001352508.2		c.*167A>G		3_prime_UTR	Exon 7 of 7	NP_001339437.1
	LINS1	NM_001352507.2		c.*167A>G		3_prime_UTR	Exon 8 of 8	NP_001339436.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINS1	ENST00000314742.13	TSL:5 MANE Select	c.*167A>G		3_prime_UTR	Exon 7 of 7	ENSP00000318423.8	Q8NG48-1
	LINS1	ENST00000869606.1		c.*167A>G		3_prime_UTR	Exon 7 of 7	ENSP00000539665.1
	LINS1	ENST00000869607.1		c.*167A>G		3_prime_UTR	Exon 7 of 7	ENSP00000539666.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 55040 AN: 143312 Hom.: 11115 Cov.: 23

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.389

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.390 AC: 132038 AN: 338246 Hom.: 28946 Cov.: 4 AF XY: 0.390 AC XY: 69768 AN XY: 178930

African (AFR) AF: 0.255 AC: 2596 AN: 10170

American (AMR) AF: 0.218 AC: 3029 AN: 13920

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 3636 AN: 10514

East Asian (EAS) AF: 0.229 AC: 5396 AN: 23520

South Asian (SAS) AF: 0.369 AC: 13341 AN: 36130

European-Finnish (FIN) AF: 0.358 AC: 6484 AN: 18114

Middle Eastern (MID) AF: 0.363 AC: 536 AN: 1476

European-Non Finnish (NFE) AF: 0.438 AC: 89645 AN: 204796

Other (OTH) AF: 0.376 AC: 7375 AN: 19606

GnomAD4 genome AF: 0.384 AC: 55049 AN: 143386 Hom.: 11115 Cov.: 23 AF XY: 0.381 AC XY: 26322 AN XY: 69170

African (AFR) AF: 0.282 AC: 10744 AN: 38092

American (AMR) AF: 0.284 AC: 3984 AN: 14010

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1379 AN: 3420

East Asian (EAS) AF: 0.236 AC: 1152 AN: 4878

South Asian (SAS) AF: 0.369 AC: 1642 AN: 4450

European-Finnish (FIN) AF: 0.413 AC: 3602 AN: 8730

Middle Eastern (MID) AF: 0.429 AC: 120 AN: 280

European-Non Finnish (NFE) AF: 0.469 AC: 31279 AN: 66662

Other (OTH) AF: 0.388 AC: 762 AN: 1966

Alfa AF: 0.402 Hom.: 1561

Bravo AF: 0.361

Asia WGS AF: 0.280 AC: 967 AN: 3452

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.37
PhyloP100		-2.0
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: rs3751552; hg19: chr15-101109276;