Genetic Variant CARMIL1:c.962-127C>T (chr6-25488355-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017640.6(CARMIL1):c.962-127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 748,486 control chromosomes in the GnomAD database, including 2,179 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.059 ( 337 hom., cov: 32)

Exomes 𝑓: 0.070 ( 1842 hom. )

Consequence

CARMIL1
NM_017640.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.362

Publications

23 publications found

Variant links:

Genes affected

CARMIL1 (HGNC:21581): (capping protein regulator and myosin 1 linker 1) Involved in several processes, including actin filament network formation; plasma membrane bounded cell projection organization; and positive regulation of cellular component organization. Located in several cellular components, including lamellipodium; macropinosome; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

CARMIL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017640.6. 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
	CARMIL1	NM_017640.6	MANE Select	c.962-127C>T		intron	N/A	NP_060110.4
	CARMIL1	NM_001173977.2		c.962-127C>T		intron	N/A	NP_001167448.1	A0A8V8TRE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CARMIL1	ENST00000329474.7	TSL:1 MANE Select	c.962-127C>T	intron	N/A	ENSP00000331983.6	Q5VZK9-1
CARMIL1	ENST00000865798.1		c.962-127C>T	intron	N/A	ENSP00000535857.1
CARMIL1	ENST00000911480.1		c.962-127C>T	intron	N/A	ENSP00000581539.1

Frequencies

GnomAD3 genomes

AF:

0.0588

AC:

8944

AN:

152142

Hom.:

336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0543

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.0277

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0947

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0882

Gnomad OTH

AF:

0.0565

GnomAD4 exome

AF:

0.0700

AC:

41740

AN:

596226

Hom.:

1842

AF XY:

0.0673

AC XY:

21591

AN XY:

320658

show subpopulations

African (AFR)

AF:

0.0155

AC:

261

AN:

16804

American (AMR)

AF:

0.0591

AC:

2197

AN:

37168

Ashkenazi Jewish (ASJ)

AF:

0.0226

AC:

419

AN:

18502

East Asian (EAS)

AF:

0.0344

AC:

1210

AN:

35156

South Asian (SAS)

AF:

0.0225

AC:

1410

AN:

62646

European-Finnish (FIN)

AF:

0.0911

AC:

3994

AN:

43824

Middle Eastern (MID)

AF:

0.0304

AC:

121

AN:

3980

European-Non Finnish (NFE)

AF:

0.0866

AC:

29994

AN:

346396

Other (OTH)

AF:

0.0672

AC:

2134

AN:

31750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1870

3740

5609

7479

9349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0587

AC:

8945

AN:

152260

Hom.:

337

Cov.:

AF XY:

0.0578

AC XY:

4304

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0156

AC:

648

AN:

41582

American (AMR)

AF:

0.0543

AC:

831

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3470

East Asian (EAS)

AF:

0.0276

AC:

143

AN:

5182

South Asian (SAS)

AF:

0.0170

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0947

AC:

1004

AN:

10606

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0882

AC:

5995

AN:

67992

Other (OTH)

AF:

0.0559

AC:

118

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

422

844

1265

1687

2109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0725

Hom.:

1263

Bravo

AF:

0.0536

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.1

(source)

DANN

Benign

0.62

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over