7-95813378-TAAAAA-TAAAAAAAA

Variant names:

• chr7-95813378-T-TAAA
• rs35397709
• NM_001135556.2:c.314+54_314+56dupAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001135556.2(DYNC1I1):​c.314+54_314+56dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 0)
  • Exomes 𝑓: 0.011 (1 hom.)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00381 (538/141102) while in subpopulation EAS AF = 0.0253 (122/4824). AF 95% confidence interval is 0.0216. There are 5 homozygotes in GnomAd4. There are 244 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 gene

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+54_314+56dupAAA		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.365+54_365+56dupAAA		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.365+54_365+56dupAAA		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+42insAAA		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.365+41_365+42insAAA		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.314+41_314+42insAAA		intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 537 AN: 141090 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00290

Gnomad ASJ AF: 0.000604

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.00158

Gnomad FIN AF: 0.000633

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000371

Gnomad OTH AF: 0.00463

GnomAD2 exomes AF: 0.0182 AC: 1953 AN: 107330 AF XY: 0.0163

Gnomad AFR exome AF: 0.0260

Gnomad AMR exome AF: 0.0365

Gnomad ASJ exome AF: 0.00959

Gnomad EAS exome AF: 0.0610

Gnomad FIN exome AF: 0.00838

Gnomad NFE exome AF: 0.00908

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.0108 AC: 13648 AN: 1260348 Hom.: 1 Cov.: 20 AF XY: 0.0106 AC XY: 6613 AN XY: 624374

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

African (AFR) AF: 0.0254 AC: 679 AN: 26784

American (AMR) AF: 0.0350 AC: 854 AN: 24400

Ashkenazi Jewish (ASJ) AF: 0.00910 AC: 188 AN: 20666

East Asian (EAS) AF: 0.0440 AC: 1528 AN: 34692

South Asian (SAS) AF: 0.0184 AC: 1246 AN: 67552

European-Finnish (FIN) AF: 0.00757 AC: 312 AN: 41242

Middle Eastern (MID) AF: 0.00471 AC: 23 AN: 4884

European-Non Finnish (NFE) AF: 0.00820 AC: 8103 AN: 987962

Other (OTH) AF: 0.0137 AC: 715 AN: 52166

⚠️ 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: 0.00381 AC: 538 AN: 141102 Hom.: 5 Cov.: 0 AF XY: 0.00358 AC XY: 244 AN XY: 68134

African (AFR) AF: 0.00840 AC: 326 AN: 38788

American (AMR) AF: 0.00290 AC: 41 AN: 14142

Ashkenazi Jewish (ASJ) AF: 0.000604 AC: 2 AN: 3312

East Asian (EAS) AF: 0.0253 AC: 122 AN: 4824

South Asian (SAS) AF: 0.00182 AC: 8 AN: 4404

European-Finnish (FIN) AF: 0.000633 AC: 5 AN: 7900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.000371 AC: 24 AN: 64632

Other (OTH) AF: 0.00512 AC: 10 AN: 1952

Alfa AF: 0.00 Hom.: 196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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;