2-241034585-C-G

Variant names:

• chr2-241034585-C-G
• rs6736167
• NM_001080437.3:c.660C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080437.3(SNED1):​c.660C>G​(p.Gly220Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,603,866 control chromosomes in the GnomAD database, including 359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (191 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (168 hom.)
• Consequence: SNED1 NM_001080437.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.19
• Publications: 1 publications found

Genes affected

SNED1 (HGNC:24696): (sushi, nidogen and EGF like domains 1) Predicted to enable Notch binding activity. Predicted to be involved in cell-matrix adhesion. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SNED1-AS1 (HGNC:41060): (SNED1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-241034585-C-G is Benign according to our data. Variant chr2-241034585-C-G is described in ClinVar as Benign. ClinVar VariationId is 775838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080437.3. 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
	SNED1	NM_001080437.3	MANE Select	c.660C>G	p.Gly220Gly	synonymous	Exon 4 of 32	NP_001073906.1	Q8TER0-1
	SNED1-AS1	NR_187211.1		n.40-982G>C		intron	N/A
	SNED1-AS1	NR_187212.1		n.40-982G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNED1	ENST00000310397.13	TSL:5 MANE Select	c.660C>G	p.Gly220Gly	synonymous	Exon 4 of 32	ENSP00000308893.8	Q8TER0-1
	SNED1	ENST00000957411.1		c.660C>G	p.Gly220Gly	synonymous	Exon 4 of 32	ENSP00000627470.1
	SNED1	ENST00000957409.1		c.660C>G	p.Gly220Gly	synonymous	Exon 4 of 31	ENSP00000627468.1

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4093 AN: 152188 Hom.: 190 Cov.: 33

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00691 AC: 1666 AN: 240978 AF XY: 0.00494

Gnomad AFR exome AF: 0.0974

Gnomad AMR exome AF: 0.00437

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000360

Gnomad OTH exome AF: 0.00275

GnomAD4 exome AF: 0.00281 AC: 4076 AN: 1451560 Hom.: 168 Cov.: 31 AF XY: 0.00240 AC XY: 1729 AN XY: 720890

African (AFR) AF: 0.101 AC: 3347 AN: 33300

American (AMR) AF: 0.00459 AC: 203 AN: 44196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25682

East Asian (EAS) AF: 0.00 AC: 0 AN: 39444

South Asian (SAS) AF: 0.000176 AC: 15 AN: 85330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51842

Middle Eastern (MID) AF: 0.00471 AC: 27 AN: 5728

European-Non Finnish (NFE) AF: 0.000132 AC: 146 AN: 1106124

Other (OTH) AF: 0.00564 AC: 338 AN: 59914

GnomAD4 genome AF: 0.0269 AC: 4100 AN: 152306 Hom.: 191 Cov.: 33 AF XY: 0.0259 AC XY: 1930 AN XY: 74482

African (AFR) AF: 0.0942 AC: 3912 AN: 41546

American (AMR) AF: 0.00797 AC: 122 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68028

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.00152 Hom.: 0

Bravo AF: 0.0304

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.37
DANN	Benign	0.64
PhyloP100		-3.2
Mutation Taster		=99/1	polymorphism (auto)

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: rs6736167; hg19: chr2-241974002;