7-95813378-TAAAAA-TAAAAAAA

Variant names:

• chr7-95813378-T-TAA
• rs35397709
• NM_001135556.2:c.314+55_314+56dupAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001135556.2(DYNC1I1):​c.314+55_314+56dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3163 hom., cov: 0)
  • Exomes 𝑓: 0.14 (582 hom.)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.299
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 7-95813378-T-TAA is Benign according to our data. Variant chr7-95813378-T-TAA is described in ClinVar as Benign. ClinVar VariationId is 1283591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 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.314+55_314+56dupAA		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.365+55_365+56dupAA		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.365+55_365+56dupAA		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.314+41_314+42insAA		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.365+41_365+42insAA		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.314+41_314+42insAA		intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 27937 AN: 140896 Hom.: 3152 Cov.: 0

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.0343

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.185

GnomAD2 exomes AF: 0.129 AC: 13861 AN: 107330 AF XY: 0.123

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.0931

Gnomad EAS exome AF: 0.257

Gnomad FIN exome AF: 0.0973

Gnomad NFE exome AF: 0.0879

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.135 AC: 167571 AN: 1239034 Hom.: 582 Cov.: 20 AF XY: 0.135 AC XY: 82639 AN XY: 613684

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.204 AC: 5385 AN: 26404

American (AMR) AF: 0.232 AC: 5568 AN: 23974

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2144 AN: 20296

East Asian (EAS) AF: 0.266 AC: 9056 AN: 34020

South Asian (SAS) AF: 0.155 AC: 10259 AN: 66326

European-Finnish (FIN) AF: 0.108 AC: 4351 AN: 40388

Middle Eastern (MID) AF: 0.0999 AC: 482 AN: 4826

European-Non Finnish (NFE) AF: 0.127 AC: 123106 AN: 971520

Other (OTH) AF: 0.141 AC: 7220 AN: 51280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.198 AC: 27962 AN: 140906 Hom.: 3163 Cov.: 0 AF XY: 0.204 AC XY: 13896 AN XY: 68024

African (AFR) AF: 0.239 AC: 9235 AN: 38712

American (AMR) AF: 0.303 AC: 4279 AN: 14118

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 431 AN: 3310

East Asian (EAS) AF: 0.422 AC: 2032 AN: 4816

South Asian (SAS) AF: 0.243 AC: 1068 AN: 4396

European-Finnish (FIN) AF: 0.146 AC: 1150 AN: 7888

Middle Eastern (MID) AF: 0.109 AC: 30 AN: 274

European-Non Finnish (NFE) AF: 0.145 AC: 9336 AN: 64572

Other (OTH) AF: 0.191 AC: 371 AN: 1946

Alfa AF: 0.0481 Hom.: 196

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35397709; hg19: chr7-95442690; COSMIC: COSV61456419; COSMIC: COSV61456419;