6-25394445-A-T

Variant names:

• chr6-25394445-A-T
• rs2149228
• NM_017640.6:c.139-25669A>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.139-25669A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,284 control chromosomes in the GnomAD database, including 1,654 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 0.14 (1654 hom., cov: 32)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 1 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]

CMAHP (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.139-25669A>T		intron_variant	Intron 2 of 36	ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.139-25669A>T		intron_variant	Intron 2 of 36	1	NM_017640.6	ENSP00000331983.6

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20797 AN: 152164 Hom.: 1647 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.137 AC: 20804 AN: 152284 Hom.: 1654 Cov.: 32 AF XY: 0.135 AC XY: 10019 AN XY: 74468

African (AFR) AF: 0.0855 AC: 3554 AN: 41560

American (AMR) AF: 0.222 AC: 3392 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3472

East Asian (EAS) AF: 0.316 AC: 1639 AN: 5182

South Asian (SAS) AF: 0.148 AC: 717 AN: 4830

European-Finnish (FIN) AF: 0.0795 AC: 844 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9731 AN: 68012

Other (OTH) AF: 0.154 AC: 324 AN: 2110

Alfa AF: 0.135 Hom.: 182

Bravo AF: 0.146

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.1
DANN	Benign	0.77
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2149228; hg19: chr6-25394673;