rs1048666

Variant names:

• chr7-96039352-C-A
• rs1048666
• NM_001135556.2:c.1440C>A

Variant summary

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

The NM_001135556.2(DYNC1I1):​c.1440C>A​(p.Gly480Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,613,652 control chromosomes in the GnomAD database, including 36,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3818 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33063 hom.)
• Consequence: DYNC1I1 NM_001135556.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.04
• Publications: 10 publications found

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-96039352-C-A is Benign according to our data. Variant chr7-96039352-C-A is described in ClinVar as Benign. ClinVar VariationId is 402811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135556.2. 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
	DYNC1I1	NM_001135556.2	MANE Select	c.1440C>A	p.Gly480Gly	synonymous	Exon 14 of 17	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.1491C>A	p.Gly497Gly	synonymous	Exon 14 of 17	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.1431C>A	p.Gly477Gly	synonymous	Exon 13 of 16	NP_001265350.1	O14576-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.1440C>A	p.Gly480Gly	synonymous	Exon 14 of 17	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.1491C>A	p.Gly497Gly	synonymous	Exon 14 of 17	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.1440C>A	p.Gly480Gly	synonymous	Exon 14 of 17	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33487 AN: 152040 Hom.: 3818 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.241

GnomAD2 exomes AF: 0.199 AC: 49833 AN: 250910 AF XY: 0.195

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.310

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.215

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.208 AC: 303451 AN: 1461494 Hom.: 33063 Cov.: 33 AF XY: 0.204 AC XY: 148371 AN XY: 727054

African (AFR) AF: 0.240 AC: 8018 AN: 33452

American (AMR) AF: 0.156 AC: 6975 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 7468 AN: 26128

East Asian (EAS) AF: 0.297 AC: 11770 AN: 39660

South Asian (SAS) AF: 0.0903 AC: 7786 AN: 86224

European-Finnish (FIN) AF: 0.182 AC: 9708 AN: 53416

Middle Eastern (MID) AF: 0.225 AC: 1296 AN: 5764

European-Non Finnish (NFE) AF: 0.214 AC: 237859 AN: 1111794

Other (OTH) AF: 0.208 AC: 12571 AN: 60376

GnomAD4 genome AF: 0.220 AC: 33492 AN: 152158 Hom.: 3818 Cov.: 33 AF XY: 0.218 AC XY: 16208 AN XY: 74388

African (AFR) AF: 0.233 AC: 9647 AN: 41490

American (AMR) AF: 0.210 AC: 3213 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1630 AN: 5170

South Asian (SAS) AF: 0.102 AC: 490 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1977 AN: 10604

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14581 AN: 68000

Other (OTH) AF: 0.239 AC: 504 AN: 2110

Alfa AF: 0.220 Hom.: 2332

Bravo AF: 0.227

Asia WGS AF: 0.195 AC: 680 AN: 3478

EpiCase AF: 0.221

EpiControl AF: 0.225

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.4
DANN	Benign	0.59
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs1048666; hg19: chr7-95668664; COSMIC: COSV100267707;