rs6793110

Variant names:

• chr3-66394191-G-A
• rs6793110
• NM_015541.3:c.1317C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015541.3(LRIG1):​c.1317C>T​(p.Ser439Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,593,816 control chromosomes in the GnomAD database, including 50,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7842 hom., cov: 33)
  • Exomes 𝑓: 0.24 (43073 hom.)
• Consequence: LRIG1 NM_015541.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.312
• Publications: 25 publications found

Genes affected

LRIG1 (HGNC:17360): (leucine rich repeats and immunoglobulin like domains 1) Predicted to act upstream of or within several processes, including innervation; otolith morphogenesis; and sensory perception of sound. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-66394191-G-A is Benign according to our data. Variant chr3-66394191-G-A is described in ClinVar as Benign. ClinVar VariationId is 403056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.312 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015541.3. 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
	LRIG1	NM_015541.3	MANE Select	c.1317C>T	p.Ser439Ser	synonymous	Exon 12 of 19	NP_056356.2	Q96JA1-1
	LRIG1	NM_001377344.1		c.1242C>T	p.Ser414Ser	synonymous	Exon 11 of 18	NP_001364273.1
	LRIG1	NM_001377345.1		c.537C>T	p.Ser179Ser	synonymous	Exon 12 of 19	NP_001364274.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIG1	ENST00000273261.8	TSL:1 MANE Select	c.1317C>T	p.Ser439Ser	synonymous	Exon 12 of 19	ENSP00000273261.3	Q96JA1-1
	LRIG1	ENST00000383703.3	TSL:1	c.1389C>T	p.Ser463Ser	synonymous	Exon 13 of 20	ENSP00000373208.3	Q96JA1-2
	LRIG1	ENST00000895940.1		c.1392C>T	p.Ser464Ser	synonymous	Exon 13 of 20	ENSP00000565999.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45691 AN: 152042 Hom.: 7822 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0722

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.276

GnomAD2 exomes AF: 0.258 AC: 59760 AN: 231390 AF XY: 0.249

Gnomad AFR exome AF: 0.463

Gnomad AMR exome AF: 0.374

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.0781

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.237 AC: 341994 AN: 1441656 Hom.: 43073 Cov.: 33 AF XY: 0.235 AC XY: 168349 AN XY: 716058

African (AFR) AF: 0.462 AC: 15051 AN: 32594

American (AMR) AF: 0.371 AC: 15425 AN: 41600

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 3453 AN: 24424

East Asian (EAS) AF: 0.0612 AC: 2417 AN: 39510

South Asian (SAS) AF: 0.213 AC: 17597 AN: 82764

European-Finnish (FIN) AF: 0.301 AC: 15894 AN: 52736

Middle Eastern (MID) AF: 0.197 AC: 1094 AN: 5556

European-Non Finnish (NFE) AF: 0.234 AC: 257603 AN: 1103050

Other (OTH) AF: 0.227 AC: 13460 AN: 59422

GnomAD4 genome AF: 0.301 AC: 45758 AN: 152160 Hom.: 7842 Cov.: 33 AF XY: 0.300 AC XY: 22318 AN XY: 74370

African (AFR) AF: 0.461 AC: 19143 AN: 41500

American (AMR) AF: 0.318 AC: 4870 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.0722 AC: 374 AN: 5182

South Asian (SAS) AF: 0.202 AC: 977 AN: 4832

European-Finnish (FIN) AF: 0.300 AC: 3166 AN: 10568

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15947 AN: 67996

Other (OTH) AF: 0.272 AC: 576 AN: 2114

Alfa AF: 0.253 Hom.: 12895

Bravo AF: 0.309

Asia WGS AF: 0.174 AC: 607 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	LRIG1-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs6793110; hg19: chr3-66444615; COSMIC: COSV56237823;