chr7-96080354-C-A

Variant names:

• chr7-96080354-C-A
• rs42082
• NM_001135556.2:c.1651-9C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001135556.2(DYNC1I1):​c.1651-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,592,128 control chromosomes in the GnomAD database, including 202,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16698 hom., cov: 33)
  • Exomes 𝑓: 0.50 (185565 hom.)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Scores: Splicing: ADA: 0.0009816
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0410
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-96080354-C-A is Benign according to our data. Variant chr7-96080354-C-A is described in ClinVar as Benign. ClinVar VariationId is 402812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 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.1651-9C>A		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.1702-9C>A		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.1642-9C>A		intron	N/A	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.1651-9C>A		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.1702-9C>A		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.1651-9C>A		intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69617 AN: 151900 Hom.: 16705 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.480 AC: 111667 AN: 232724 AF XY: 0.484

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.561

Gnomad FIN exome AF: 0.508

Gnomad NFE exome AF: 0.524

Gnomad OTH exome AF: 0.516

GnomAD4 exome AF: 0.505 AC: 726597 AN: 1440112 Hom.: 185565 Cov.: 43 AF XY: 0.502 AC XY: 359320 AN XY: 715134

African (AFR) AF: 0.308 AC: 10004 AN: 32458

American (AMR) AF: 0.384 AC: 15639 AN: 40684

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 15050 AN: 24444

East Asian (EAS) AF: 0.526 AC: 20805 AN: 39560

South Asian (SAS) AF: 0.395 AC: 32371 AN: 82014

European-Finnish (FIN) AF: 0.510 AC: 26860 AN: 52662

Middle Eastern (MID) AF: 0.538 AC: 3014 AN: 5604

European-Non Finnish (NFE) AF: 0.519 AC: 572618 AN: 1103306

Other (OTH) AF: 0.509 AC: 30236 AN: 59380

GnomAD4 genome AF: 0.458 AC: 69609 AN: 152016 Hom.: 16698 Cov.: 33 AF XY: 0.457 AC XY: 33945 AN XY: 74316

African (AFR) AF: 0.314 AC: 13042 AN: 41472

American (AMR) AF: 0.460 AC: 7034 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2078 AN: 3464

East Asian (EAS) AF: 0.545 AC: 2806 AN: 5146

South Asian (SAS) AF: 0.399 AC: 1923 AN: 4820

European-Finnish (FIN) AF: 0.516 AC: 5448 AN: 10552

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35426 AN: 67968

Other (OTH) AF: 0.496 AC: 1045 AN: 2108

Alfa AF: 0.487 Hom.: 6273

Bravo AF: 0.453

Asia WGS AF: 0.485 AC: 1687 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DYNC1I1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.2
DANN	Benign	0.60
PhyloP100		-0.041
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00098
dbscSNV1_RF	Benign	0.084
SpliceAI score (max)		0.010		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: rs42082; hg19: chr7-95709666; COSMIC: COSV61455011;