rs2276650

Variant names:

• chr2-96195421-C-G
• rs2276650
• NM_020151.4:c.419G>C
• STARD7 p.Arg140Pro

Your query was ambiguous. Multiple possible variants found:

• chr2-96195421-C-G
• chr2-96195421-C-T

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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. 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
• Publications: 24 publications found

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]

STARD7 Gene-Disease associations (from GenCC):

• epilepsy, familial adult myoclonic, 2

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020151.4. 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
	STARD7	NM_020151.4	MANE Select	c.419G>C	p.Arg140Pro	missense	Exon 2 of 8	NP_064536.2	Q9NQZ5
	STARD7	NM_001385622.1		c.116G>C	p.Arg39Pro	missense	Exon 2 of 8	NP_001372551.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD7	ENST00000337288.10	TSL:1 MANE Select	c.419G>C	p.Arg140Pro	missense	Exon 2 of 8	ENSP00000338030.5	Q9NQZ5
	STARD7	ENST00000869793.1		c.512G>C	p.Arg171Pro	missense	Exon 3 of 9	ENSP00000539852.1
	STARD7	ENST00000914443.1		c.419G>C	p.Arg140Pro	missense	Exon 2 of 8	ENSP00000584502.1

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

GnomAD2 exomes AF: 0.151 AC: 37184 AN: 246030 AF XY: 0.157

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 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

African (AFR) AF: 0.0636 AC: 2128 AN: 33464

American (AMR) AF: 0.121 AC: 5350 AN: 44316

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4111 AN: 26020

East Asian (EAS) AF: 0.111 AC: 4410 AN: 39646

South Asian (SAS) AF: 0.228 AC: 19486 AN: 85572

European-Finnish (FIN) AF: 0.146 AC: 7792 AN: 53226

Middle Eastern (MID) AF: 0.222 AC: 1276 AN: 5758

European-Non Finnish (NFE) AF: 0.165 AC: 183759 AN: 1110400

Other (OTH) AF: 0.169 AC: 10177 AN: 60284

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

African (AFR) AF: 0.0625 AC: 2597 AN: 41556

American (AMR) AF: 0.155 AC: 2372 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3470

East Asian (EAS) AF: 0.111 AC: 577 AN: 5178

South Asian (SAS) AF: 0.218 AC: 1049 AN: 4818

European-Finnish (FIN) AF: 0.141 AC: 1498 AN: 10598

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11404 AN: 68010

Other (OTH) AF: 0.170 AC: 360 AN: 2114

Alfa AF: 0.149 Hom.: 1453

Bravo AF: 0.128

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.071	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.97	N
PhyloP100		2.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.7	N
REVEL	Uncertain	0.32
Sift	Benign	1.0	T
Sift4G	Benign	0.77	T
Varity_R		0.11
gMVP		0.40
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2276650;

hg19: chr2-96861159;

COSMIC: COSV61525305;

COSMIC: COSV61525305;