chr17-16453005-T-C

Variant names:

• chr17-16453005-T-C
• rs8082268
• NM_001113567.3:c.376-5045A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113567.3(LRRC75A):​c.376-5045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 151,774 control chromosomes in the GnomAD database, including 28,693 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (28693 hom., cov: 30)
• Consequence: LRRC75A NM_001113567.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 3 publications found

Genes affected

LRRC75A (HGNC:32403): (leucine rich repeat containing 75A) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SNHG29 (HGNC:28619): (small nucleolar RNA host gene 29)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113567.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC75A	NM_001113567.3	MANE Select	c.376-5045A>G		intron	N/A	NP_001107039.1
	LRRC75A	NM_207387.4		c.376-8874A>G		intron	N/A	NP_997270.2
	SNHG29	NR_027171.1		n.554+11875T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC75A	ENST00000470794.2	TSL:1 MANE Select	c.376-5045A>G		intron	N/A	ENSP00000419502.1
	SNHG29	ENST00000581361.5	TSL:1	n.182-7888T>C		intron	N/A
	LRRC75A	ENST00000409083.7	TSL:2	c.376-8874A>G		intron	N/A	ENSP00000386504.3

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92154 AN: 151652 Hom.: 28671 Cov.: 30

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.598

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.608 AC: 92218 AN: 151774 Hom.: 28693 Cov.: 30 AF XY: 0.603 AC XY: 44692 AN XY: 74132

African (AFR) AF: 0.594 AC: 24594 AN: 41370

American (AMR) AF: 0.535 AC: 8161 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2304 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1367 AN: 5108

South Asian (SAS) AF: 0.451 AC: 2161 AN: 4796

European-Finnish (FIN) AF: 0.633 AC: 6666 AN: 10528

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45056 AN: 67938

Other (OTH) AF: 0.597 AC: 1261 AN: 2112

Alfa AF: 0.641 Hom.: 3891

Bravo AF: 0.595

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.81
PhyloP100		-0.72
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: rs8082268; hg19: chr17-16356319; COSMIC: COSV69125195; COSMIC: COSV69125195;