15-70991450-T-C

Variant names:

• chr15-70991450-T-C
• rs894128
• NM_017691.5:c.1169+7193T>C

Variant summary

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

The NM_017691.5(LRRC49):​c.1169+7193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 152,302 control chromosomes in the GnomAD database, including 70,675 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 0.96 (70675 hom., cov: 32)
• Consequence: LRRC49 NM_017691.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 1 publications found

Genes affected

LRRC49 (HGNC:25965): (leucine rich repeat containing 49) Predicted to be involved in outer dynein arm assembly. Predicted to be located in microtubule. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017691.5. 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
	LRRC49	NM_017691.5	MANE Select	c.1169+7193T>C		intron	N/A	NP_060161.2
	LRRC49	NM_001199017.3		c.1184+7193T>C		intron	N/A	NP_001185946.1
	LRRC49	NM_001284357.2		c.1139+7193T>C		intron	N/A	NP_001271286.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC49	ENST00000260382.10	TSL:1 MANE Select	c.1169+7193T>C		intron	N/A	ENSP00000260382.4
	LRRC49	ENST00000560369.5	TSL:2	c.1184+7193T>C		intron	N/A	ENSP00000453273.1
	LRRC49	ENST00000544974.6	TSL:2	c.1139+7193T>C		intron	N/A	ENSP00000439600.2

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146468 AN: 152184 Hom.: 70628 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.963

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

GnomAD4 genome AF: 0.962 AC: 146575 AN: 152302 Hom.: 70675 Cov.: 32 AF XY: 0.963 AC XY: 71762 AN XY: 74482

African (AFR) AF: 0.892 AC: 37028 AN: 41534

American (AMR) AF: 0.984 AC: 15060 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 3376 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 0.990 AC: 4782 AN: 4828

European-Finnish (FIN) AF: 0.995 AC: 10572 AN: 10626

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.990 AC: 67352 AN: 68038

Other (OTH) AF: 0.964 AC: 2037 AN: 2114

Alfa AF: 0.961 Hom.: 10324

Bravo AF: 0.959

Asia WGS AF: 0.990 AC: 3442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.65
DANN	Benign	0.58
PhyloP100		-1.8
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: rs894128; hg19: chr15-71283789;