rs7

Positions:

• chr7-92150243-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

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

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 971 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRD1	NM_001161528.2	c.2278+291A>T		intron_variant		ENST00000458448.6	NP_001155000.1
CYP51A1-AS1	NR_122109.1	n.1038+7509T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRD1	ENST00000458448.6	c.2278+291A>T		intron_variant		5	NM_001161528.2	ENSP00000405987	P1
LRRD1	ENST00000343318.9	c.331+291A>T		intron_variant		1		ENSP00000339642
CYP51A1-AS1	ENST00000453068.1	n.997+7509T>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0301

Gnomad4 FIN AF: 0.0158

Gnomad4 NFE AF: 0.00822

Gnomad4 OTH AF: 0.00758

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7; hg19: chr7-91779557;