rs17492120

Variant names:

• chr6-25590083-C-T
• rs17492120
• NM_017640.6:c.3007-4332C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017640.6(CARMIL1):​c.3007-4332C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 152,252 control chromosomes in the GnomAD database, including 616 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 0.079 (616 hom., cov: 33)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 8 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.3007-4332C>T		intron_variant	Intron 31 of 36	ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.3007-4332C>T		intron_variant	Intron 31 of 36	1	NM_017640.6	ENSP00000331983.6
CARMIL1	ENST00000700669.1	c.3007-4332C>T		intron_variant	Intron 31 of 36			ENSP00000515137.1
CARMIL1	ENST00000635618.1	n.1807-4332C>T		intron_variant	Intron 18 of 25	5		ENSP00000489114.1

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11964 AN: 152134 Hom.: 616 Cov.: 33

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0860

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0785 AC: 11957 AN: 152252 Hom.: 616 Cov.: 33 AF XY: 0.0770 AC XY: 5732 AN XY: 74434

African (AFR) AF: 0.0209 AC: 867 AN: 41562

American (AMR) AF: 0.0794 AC: 1213 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3472

East Asian (EAS) AF: 0.0278 AC: 144 AN: 5172

South Asian (SAS) AF: 0.0508 AC: 245 AN: 4820

European-Finnish (FIN) AF: 0.101 AC: 1075 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8022 AN: 68024

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.104 Hom.: 540

Bravo AF: 0.0744

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17492120; hg19: chr6-25590311;