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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARMIL1	NM_017640.6 link	c.962-127C>T		intron_variant	Intron 12 of 36	ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7 link	c.962-127C>T		intron_variant	Intron 12 of 36	1	NM_017640.6	ENSP00000331983.6
CARMIL1	ENST00000700669.1 link	c.962-127C>T		intron_variant	Intron 12 of 36			ENSP00000515137.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over