rs2721172

Variant names:

• chr8-144519798-T-C
• rs2721172
• NM_014665.4:c.73T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144519798-T-C
• chr8-144519798-T-A
• chr8-144519798-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014665.4(LRRC14):​c.73T>C​(p.Leu25Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,613,306 control chromosomes in the GnomAD database, including 790,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74288 hom., cov: 36)
  • Exomes 𝑓: 0.99 (716513 hom.)
• Consequence: LRRC14 NM_014665.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.222
• Publications: 14 publications found

Genes affected

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 8-144519798-T-C is Benign according to our data. Variant chr8-144519798-T-C is described in ClinVar as Benign. ClinVar VariationId is 403369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.222 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014665.4. 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
	LRRC14	NM_014665.4	MANE Select	c.73T>C	p.Leu25Leu	synonymous	Exon 2 of 4	NP_055480.1	Q15048
	LRRC14	NM_001272036.2		c.73T>C	p.Leu25Leu	synonymous	Exon 3 of 5	NP_001258965.1	Q15048

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.73T>C	p.Leu25Leu	synonymous	Exon 2 of 4	ENSP00000292524.1	Q15048
	LRRC14	ENST00000529022.5	TSL:1	c.73T>C	p.Leu25Leu	synonymous	Exon 3 of 5	ENSP00000434768.1	Q15048
	LRRC14	ENST00000887351.1		c.73T>C	p.Leu25Leu	synonymous	Exon 3 of 5	ENSP00000557410.1

Frequencies

GnomAD3 genomes AF: 0.987 AC: 150218 AN: 152246 Hom.: 74231 Cov.: 36

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.998

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.989

GnomAD2 exomes AF: 0.970 AC: 242698 AN: 250128 AF XY: 0.976

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.902

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.796

Gnomad FIN exome AF: 0.997

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.982

GnomAD4 exome AF: 0.989 AC: 1445313 AN: 1460942 Hom.: 716513 Cov.: 78 AF XY: 0.990 AC XY: 719452 AN XY: 726770

African (AFR) AF: 0.998 AC: 33418 AN: 33480

American (AMR) AF: 0.908 AC: 40600 AN: 44708

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26135 AN: 26136

East Asian (EAS) AF: 0.744 AC: 29524 AN: 39700

South Asian (SAS) AF: 0.999 AC: 86130 AN: 86258

European-Finnish (FIN) AF: 0.996 AC: 52319 AN: 52510

Middle Eastern (MID) AF: 0.999 AC: 5760 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111720 AN: 1112000

Other (OTH) AF: 0.989 AC: 59707 AN: 60382

GnomAD4 genome AF: 0.987 AC: 150334 AN: 152364 Hom.: 74288 Cov.: 36 AF XY: 0.985 AC XY: 73385 AN XY: 74500

African (AFR) AF: 0.997 AC: 41456 AN: 41590

American (AMR) AF: 0.951 AC: 14565 AN: 15312

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.795 AC: 4115 AN: 5174

South Asian (SAS) AF: 0.997 AC: 4818 AN: 4834

European-Finnish (FIN) AF: 0.998 AC: 10608 AN: 10632

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68001 AN: 68028

Other (OTH) AF: 0.989 AC: 2093 AN: 2116

Alfa AF: 0.997 Hom.: 37541

Bravo AF: 0.982

Asia WGS AF: 0.943 AC: 3280 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.8
DANN	Benign	0.78
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2721172; hg19: chr8-145745182; COSMIC: COSV52881411; COSMIC: COSV52881411;