8-85110101-CT-C

Variant names:

• chr8-85110101-CT-C
• rs755909227
• NM_033402.5:c.311-3delT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_033402.5(LRRCC1):​c.311-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 770,880 control chromosomes in the GnomAD database, including 10 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 33)
  • Exomes 𝑓: 0.058 (8 hom.)
• Consequence: LRRCC1 NM_033402.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.363
• Publications: 0 publications found

Genes affected

LRRCC1 (HGNC:29373): (leucine rich repeat and coiled-coil centrosomal protein 1) This gene encodes a centrosomal protein that maintains the structural integrity of the centrosome and plays a key role in mitotic spindle formation. The encoded protein contains an N-terminal leucine-rich repeat domain and a C-terminal coiled-coil domain. It associates with the centrosome throughout the cell cycle and accumulates on the mitotic centrosome. [provided by RefSeq, Mar 2017]

E2F5-DT (HGNC:55393): (E2F5 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 8-85110101-CT-C is Benign according to our data. Variant chr8-85110101-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1669647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033402.5. 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
	LRRCC1	NM_033402.5	MANE Select	c.311-3delT		splice_region intron	N/A	NP_208325.3
	LRRCC1	NM_001349636.2		c.32-3delT		splice_region intron	N/A	NP_001336565.1
	LRRCC1	NM_001349637.2		c.-158-3delT		splice_region intron	N/A	NP_001336566.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRCC1	ENST00000360375.8	TSL:1 MANE Select	c.311-13delT		intron	N/A	ENSP00000353538.3	Q9C099-1
	LRRCC1	ENST00000414626.2	TSL:1	c.251-13delT		intron	N/A	ENSP00000394695.2	Q9C099-2
	LRRCC1	ENST00000517875.5	TSL:1	n.105-13delT		intron	N/A	ENSP00000430960.1	E5RGA4

Frequencies

GnomAD3 genomes AF: 0.00390 AC: 567 AN: 145240 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00646

Gnomad ASJ AF: 0.00207

Gnomad EAS AF: 0.000399

Gnomad SAS AF: 0.000863

Gnomad FIN AF: 0.00336

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00521

Gnomad OTH AF: 0.00816

GnomAD2 exomes AF: 0.0910 AC: 6071 AN: 66706 AF XY: 0.0944

Gnomad AFR exome AF: 0.0617

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.0805

Gnomad FIN exome AF: 0.0839

Gnomad NFE exome AF: 0.0884

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.0581 AC: 36374 AN: 625584 Hom.: 8 Cov.: 8 AF XY: 0.0584 AC XY: 18793 AN XY: 321566

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0537 AC: 739 AN: 13770

American (AMR) AF: 0.0555 AC: 958 AN: 17258

Ashkenazi Jewish (ASJ) AF: 0.0589 AC: 727 AN: 12348

East Asian (EAS) AF: 0.0482 AC: 1032 AN: 21424

South Asian (SAS) AF: 0.0672 AC: 2660 AN: 39594

European-Finnish (FIN) AF: 0.0537 AC: 1646 AN: 30660

Middle Eastern (MID) AF: 0.0446 AC: 112 AN: 2514

European-Non Finnish (NFE) AF: 0.0583 AC: 26886 AN: 461104

Other (OTH) AF: 0.0600 AC: 1614 AN: 26912

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00391 AC: 568 AN: 145296 Hom.: 2 Cov.: 33 AF XY: 0.00370 AC XY: 261 AN XY: 70632

African (AFR) AF: 0.00175 AC: 70 AN: 39978

American (AMR) AF: 0.00652 AC: 95 AN: 14572

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 7 AN: 3374

East Asian (EAS) AF: 0.000400 AC: 2 AN: 4998

South Asian (SAS) AF: 0.000867 AC: 4 AN: 4616

European-Finnish (FIN) AF: 0.00336 AC: 30 AN: 8926

Middle Eastern (MID) AF: 0.00719 AC: 2 AN: 278

European-Non Finnish (NFE) AF: 0.00521 AC: 342 AN: 65686

Other (OTH) AF: 0.00810 AC: 16 AN: 1976

Alfa AF: 0.0347 Hom.: 3

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism

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: rs755909227; hg19: chr8-86022336; COSMIC: COSV64483103;