rs2276650

chr2-96195421-C-Gchr2-96195421-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020151.4(STARD7):c.419G>C(p.Arg140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,610,920 control chromosomes in the GnomAD database, including 22,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.14 (1591 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20521 hom.)
• Consequence: STARD7 NM_020151.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

Genes affected

STARD7 (HGNC:18063): (StAR related lipid transfer domain containing 7) Predicted to enable lipid binding activity. Predicted to act upstream of or within several processes, including establishment of skin barrier; mucociliary clearance; and myeloid dendritic cell activation. Predicted to be located in cytoplasm and extracellular region. Implicated in familial adult myoclonic epilepsy 2. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013928711).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STARD7	NM_020151.4	c.419G>C	p.Arg140Pro	missense_variant	2/8	ENST00000337288.10
STARD7	NM_001385622.1	c.116G>C	p.Arg39Pro	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STARD7	ENST00000337288.10	c.419G>C	p.Arg140Pro	missense_variant	2/8	1	NM_020151.4	P1
STARD7	ENST00000443962.1	c.116G>C	p.Arg39Pro	missense_variant	2/5	5
STARD7	ENST00000462501.1	n.94G>C		non_coding_transcript_exon_variant	1/7	2
STARD7	ENST00000488084.1	n.166G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20563 AN: 152116 Hom.: 1585 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.166

GnomAD3 exomes AF: 0.151 AC: 37184 AN: 246030 Hom.: 3128 AF XY: 0.157 AC XY: 20859 AN XY: 132892

Gnomad AFR exome AF: 0.0585

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.163 AC: 238489 AN: 1458686 Hom.: 20521 Cov.: 33 AF XY: 0.166 AC XY: 120597 AN XY: 725306

Gnomad4 AFR exome AF: 0.0636

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.135 AC: 20590 AN: 152234 Hom.: 1591 Cov.: 32 AF XY: 0.137 AC XY: 10166 AN XY: 74414

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.170

Alfa AF: 0.149 Hom.: 1453

Bravo AF: 0.128

TwinsUK AF: 0.171 AC: 635

ALSPAC AF: 0.160 AC: 615

ESP6500AA AF: 0.0667 AC: 294

ESP6500EA AF: 0.165 AC: 1418

ExAC AF: 0.149 AC: 18115

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	17
Dann	Benign	0.65
DEOGEN2	Benign	0.0055	T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.071	T;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.97	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.7	N;N
REVEL	Uncertain	0.32
Sift	Benign	1.0	T;T
Sift4G	Benign	0.77	T;.
Polyphen		0.0	B;.
Vest4		0.043
MPC		0.82
ClinPred		0.0098	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.40

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: rs2276650; hg19: chr2-96861159; COSMIC: COSV61525305; COSMIC: COSV61525305;