rs1537323

Variant names:

• chr1-54016850-T-G
• rs1537323
• NM_001010978.4:c.73+526A>C

Variant summary

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

The NM_001010978.4(LDLRAD1):​c.73+526A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,042 control chromosomes in the GnomAD database, including 17,767 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 0.48 (17767 hom., cov: 32)
• Consequence: LDLRAD1 NM_001010978.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 7 publications found

Genes affected

LDLRAD1 (HGNC:32069): (low density lipoprotein receptor class A domain containing 1) Predicted to be integral component of membrane. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD1	NM_001010978.4	c.73+526A>C		intron_variant	Intron 2 of 5	ENST00000371360.2	NP_001010978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD1	ENST00000371360.2	c.73+526A>C		intron_variant	Intron 2 of 5	1	NM_001010978.4	ENSP00000360411.1
LDLRAD1	ENST00000420619.5	c.85+1242A>C		intron_variant	Intron 1 of 3	1		ENSP00000411017.1
LDLRAD1	ENST00000545928.5	c.73+526A>C		intron_variant	Intron 2 of 4	1		ENSP00000445871.1
LDLRAD1	ENST00000371362.7	c.73+526A>C		intron_variant	Intron 2 of 3	1		ENSP00000360413.3

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72661 AN: 151924 Hom.: 17753 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.478 AC: 72714 AN: 152042 Hom.: 17767 Cov.: 32 AF XY: 0.477 AC XY: 35468 AN XY: 74318

African (AFR) AF: 0.558 AC: 23139 AN: 41458

American (AMR) AF: 0.521 AC: 7972 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1938 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3096 AN: 5166

South Asian (SAS) AF: 0.365 AC: 1760 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3866 AN: 10570

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29119 AN: 67948

Other (OTH) AF: 0.526 AC: 1114 AN: 2116

Alfa AF: 0.458 Hom.: 20278

Bravo AF: 0.500

Asia WGS AF: 0.470 AC: 1635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.60
PhyloP100		-1.9
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: rs1537323; hg19: chr1-54482523;