rs2274089

chr6-25488355-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CARMIL1	NM_017640.6	c.962-127C>T		intron_variant		ENST00000329474.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARMIL1	ENST00000329474.7	c.962-127C>T		intron_variant		1	NM_017640.6	P1
CARMIL1	ENST00000700669.1	c.962-127C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8944 AN: 152142 Hom.: 336 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0155

Gnomad4 AMR exome AF: 0.0591

Gnomad4 ASJ exome AF: 0.0226

Gnomad4 EAS exome AF: 0.0344

Gnomad4 SAS exome AF: 0.0225

Gnomad4 FIN exome AF: 0.0911

Gnomad4 NFE exome AF: 0.0866

Gnomad4 OTH exome AF: 0.0672

GnomAD4 genome AF: 0.0587 AC: 8945 AN: 152260 Hom.: 337 Cov.: 32 AF XY: 0.0578 AC XY: 4304 AN XY: 74434

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0543

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.0276

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0947

Gnomad4 NFE AF: 0.0882

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0772 Hom.: 838

Bravo AF: 0.0536

Asia WGS AF: 0.0270 AC: 94 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
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs2274089; hg19: chr6-25488583;