7-869411-G-A

Variant names:

• chr7-869411-G-A
• rs61744747
• NM_001130965.3:c.2043G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001130965.3(SUN1):​c.2043G>A​(p.Arg681Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,613,780 control chromosomes in the GnomAD database, including 731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (58 hom., cov: 32)
  • Exomes 𝑓: 0.014 (673 hom.)
• Consequence: SUN1 NM_001130965.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0520
• Publications: 9 publications found

Genes affected

SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

LOC124901568 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.035).
• BP6: Variant 7-869411-G-A is Benign according to our data. Variant chr7-869411-G-A is described in ClinVar as Benign. ClinVar VariationId is 461646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.052 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130965.3. 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
	SUN1	NM_001130965.3	MANE Select	c.2043G>A	p.Arg681Arg	synonymous	Exon 17 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.2457G>A	p.Arg819Arg	synonymous	Exon 20 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.2436G>A	p.Arg812Arg	synonymous	Exon 21 of 23	NP_001354634.1	O94901-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.2043G>A	p.Arg681Arg	synonymous	Exon 17 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000429178.5	TSL:1	c.1818G>A	p.Arg606Arg	synonymous	Exon 15 of 17	ENSP00000409909.1	H0Y742
	SUN1	ENST00000475971.5	TSL:1	n.2152G>A		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2045 AN: 152006 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00910

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.0223 AC: 5565 AN: 249268 AF XY: 0.0226

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.0176

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.0290

Gnomad NFE exome AF: 0.00889

Gnomad OTH exome AF: 0.0159

GnomAD4 exome AF: 0.0135 AC: 19754 AN: 1461656 Hom.: 673 Cov.: 31 AF XY: 0.0142 AC XY: 10350 AN XY: 727146

African (AFR) AF: 0.00131 AC: 44 AN: 33480

American (AMR) AF: 0.00320 AC: 143 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 466 AN: 26122

East Asian (EAS) AF: 0.152 AC: 6027 AN: 39694

South Asian (SAS) AF: 0.0277 AC: 2389 AN: 86258

European-Finnish (FIN) AF: 0.0275 AC: 1469 AN: 53390

Middle Eastern (MID) AF: 0.0328 AC: 189 AN: 5762

European-Non Finnish (NFE) AF: 0.00719 AC: 7997 AN: 1111862

Other (OTH) AF: 0.0171 AC: 1030 AN: 60378

GnomAD4 genome AF: 0.0134 AC: 2043 AN: 152124 Hom.: 58 Cov.: 32 AF XY: 0.0156 AC XY: 1157 AN XY: 74364

African (AFR) AF: 0.00207 AC: 86 AN: 41486

American (AMR) AF: 0.00464 AC: 71 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3468

East Asian (EAS) AF: 0.140 AC: 722 AN: 5150

South Asian (SAS) AF: 0.0262 AC: 126 AN: 4814

European-Finnish (FIN) AF: 0.0312 AC: 331 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00910 AC: 619 AN: 67990

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.00973 Hom.: 4

Bravo AF: 0.0119

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Emery-Dreifuss muscular dystrophy (1)
-	-	1	not provided (1)
-	-	1	SUN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.5
DANN	Benign	0.48
PhyloP100		-0.052
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Other links and lift over

dbSNP: rs61744747; hg19: chr7-909048; COSMIC: COSV67447896;