rs7

Variant names:

• chr7-92150243-T-A
• rs7
• NM_001161528.2:c.2278+291A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001161528.2(LRRD1):​c.2278+291A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 152,246 control chromosomes in the GnomAD database, including 10 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 0.0064 (10 hom., cov: 32)
• Consequence: LRRD1 NM_001161528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 0 publications found

Genes affected

LRRD1 (HGNC:34300): (leucine rich repeats and death domain containing 1) Predicted to be involved in positive regulation of Ras protein signal transduction and signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289027 (HGNC:):

CYP51A1-AS1 (HGNC:50694): (CYP51A1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00638 (971/152246) while in subpopulation SAS AF = 0.0301 (145/4822). AF 95% confidence interval is 0.0261. There are 10 homozygotes in GnomAd4. There are 510 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 971 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRD1	NM_001161528.2	c.2278+291A>T		intron_variant	Intron 4 of 5	ENST00000458448.6	NP_001155000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRD1	ENST00000458448.6	c.2278+291A>T		intron_variant	Intron 4 of 5	5	NM_001161528.2	ENSP00000405987.1
ENSG00000289027	ENST00000692281.1	c.2026-18371A>T		intron_variant	Intron 17 of 25			ENSP00000510568.1
ENSG00000285953	ENST00000458493.6	c.2386+291A>T		intron_variant	Intron 18 of 19	4		ENSP00000396352.2

Frequencies

GnomAD3 genomes AF: 0.00640 AC: 974 AN: 152128 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00822

Gnomad OTH AF: 0.00766

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

GnomAD4 genome AF: 0.00638 AC: 971 AN: 152246 Hom.: 10 Cov.: 32 AF XY: 0.00685 AC XY: 510 AN XY: 74438

African (AFR) AF: 0.000866 AC: 36 AN: 41554

American (AMR) AF: 0.00255 AC: 39 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.0301 AC: 145 AN: 4822

European-Finnish (FIN) AF: 0.0158 AC: 168 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00822 AC: 559 AN: 68008

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00757 Hom.: 3

Bravo AF: 0.00437

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.83
PhyloP100		0.65
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: rs7; hg19: chr7-91779557;