1-54017417-C-G

Variant names:

• chr1-54017417-C-G
• rs141274711
• NM_001010978.4:c.32G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010978.4(LDLRAD1):​c.32G>C​(p.Gly11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G11V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LDLRAD1 NM_001010978.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062662214).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010978.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD1	NM_001010978.4	MANE Select	c.32G>C	p.Gly11Ala	missense	Exon 2 of 6	NP_001010978.2	Q5T700-1
	LDLRAD1	NM_001276393.2		c.32G>C	p.Gly11Ala	missense	Exon 2 of 5	NP_001263322.1	Q5T700-4
	LDLRAD1	NM_001276394.2		c.32G>C	p.Gly11Ala	missense	Exon 2 of 4	NP_001263323.1	Q5T700-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD1	ENST00000371360.2	TSL:1 MANE Select	c.32G>C	p.Gly11Ala	missense	Exon 2 of 6	ENSP00000360411.1	Q5T700-1
	LDLRAD1	ENST00000545928.5	TSL:1	c.32G>C	p.Gly11Ala	missense	Exon 2 of 5	ENSP00000445871.1	Q5T700-4
	LDLRAD1	ENST00000371362.7	TSL:1	c.32G>C	p.Gly11Ala	missense	Exon 2 of 4	ENSP00000360413.3	Q5T700-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1450396 Hom.: 0 Cov.: 31 AF XY: 0.00000417 AC XY: 3 AN XY: 720264

African (AFR) AF: 0.00 AC: 0 AN: 33308

American (AMR) AF: 0.00 AC: 0 AN: 43366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25822

East Asian (EAS) AF: 0.00 AC: 0 AN: 39450

South Asian (SAS) AF: 0.0000238 AC: 2 AN: 83952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52806

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105994

Other (OTH) AF: 0.00 AC: 0 AN: 59948

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	1.9
DANN	Benign	0.81
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.44
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.076
Sift	Benign	0.031	D
Sift4G	Uncertain	0.047	D
Polyphen		0.22	B
Vest4		0.27
MutPred		0.070		Loss of loop (P = 0.1258)
MVP		0.13
MPC		0.059
ClinPred		0.085	T
GERP RS		0.69
Varity_R		0.045
gMVP		0.33
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141274711; hg19: chr1-54483090;