7-817715-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000457378.6(SUN1):c.43+216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,092 control chromosomes in the GnomAD database, including 6,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (6058 hom., cov: 32)
• Consequence: SUN1 ENST00000457378.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-817715-A-G is Benign according to our data. Variant chr7-817715-A-G is described in ClinVar as [Benign]. Clinvar id is 1263462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001171944.2	c.-21+1042A>G		intron_variant
SUN1	NM_001171945.2	c.43+216A>G		intron_variant
SUN1	NM_001171946.2	c.-21+2112A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000457378.6	c.43+216A>G		intron_variant		1
SUN1	ENST00000389574.7	c.-74+1042A>G		intron_variant		2		A2
SUN1	ENST00000424128.5	c.-103+216A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40200 AN: 151974 Hom.: 6057 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0926

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.265 AC: 40231 AN: 152092 Hom.: 6058 Cov.: 32 AF XY: 0.262 AC XY: 19480 AN XY: 74352

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.223

Alfa AF: 0.221 Hom.: 4823

Bravo AF: 0.270

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.2
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs4275123; hg19: chr7-857352;